propan-2-yl carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCl) was charged to a 3 L Lara vessel and dry tetrahydrofuran (THF) (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. Lithium tert-butoxide (1M, 655 mL, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 mL) were added and the mixture brought to 20° C. with vigourous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 mL) was added and the mixture stirred vigorously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The was applied to a silica column (40+M Biotage) and eluted with DCM/EtOAc (1:1 to 0:1, 10CV). The product containing fractions were evaporated to dryness and loaded on to a Redisep Isco silica column (1500 g) and eluted with a EtOAc in cyclohexane gradient (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigourous stirring to separate Brine (375 mL) was added the mixture stirred vigorously to separate The organic layer was dried (MgSO4) filtered evaporated to a brown oil (60 g) eluted with DCM/EtOAc (1:1 to 0:1, 10CV) The product containing fractions were evaporated to dryness eluted with a EtOAc in cyclohexane gradient (0-40%) The clean, product containing fractions were evaporated to an off-white solid (15.41 g)

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry THF (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. lithium tert-butoxide (1M, 655 ml, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 ml) were added and the mixture brought to 20° C. with vigorous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 ml) was added and the mixture stirred vigourously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The oil was applied to a silica column (40+M Biotage) and eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a silica column (1500 g, Redisep Isco) and eluted with a ethyl acetate in cyclohexane gradient (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C), Rt 0.68, MH+ 172 added reached −17° C. was added by peristaltic pump over 2 h the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigorous stirring to separate Brine (375 ml) was added the mixture stirred vigourously to separate The organic layer was dried (MgSO4) filtered evaporated to a brown oil (60 g) eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV) The product containing fractions were evaporated to dryness eluted with a ethyl acetate in cyclohexane gradient (0-40%) The clean, product containing fractions were evaporated to an off-white solid (15.41 g)

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry tetrahydrofuran (THF) (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. Lithium tert-butoxide (1M, 655 mL, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 mL) were added and the mixture brought to 20° C. with vigourous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 mL) was added and the mixture stirred vigourously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The was applied to a silica column (40+M Biotage) and eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a Redisep Isco silica column (1500 g) and eluted with a gradient ethyl acetate in cyclohexane (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigourous stirring to separate Brine (375 mL) was added the mixture stirred vigourously to separate The organic layer was dried (MgSO4) filtered evaporated to a brown oil (60 g) eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV) The product containing fractions were evaporated to dryness eluted with a gradient ethyl acetate in cyclohexane (0-40%) The clean, product containing fractions were evaporated to an off-white solid (15.41 g)

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry tetrahydrofuran (THF) (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. Lithium tert-butoxide (1M, 655 mL, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 mL) were added and the mixture brought to 20° C. with vigourous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 mL) was added and the mixture stirred vigourously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The was applied to a silica column (40+M Biotage) and eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a Redisep Isco silica column (1500 g) and eluted with a gradient ethyl acetate in cyclohexane (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigourous stirring to separate Brine (375 mL) was added the mixture stirred vigourously to separate The organic layer was dried (MgSO4) filtered evaporated to a brown oil (60 g) eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV) The product containing fractions were evaporated to dryness eluted with a gradient ethyl acetate in cyclohexane (0-40%) The clean, product containing fractions were evaporated to an off-white solid (15.41 g)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry THF (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. lithium tert-butoxide (1M, 655 ml, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 ml) were added and the mixture brought to 20° C. with vigorous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 ml) was added and the mixture stirred vigourously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The oil was applied to a silica column (40+M Biotage) and eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a silica column (1500 g, Redisep Isco) and eluted with a ethyl acetate in cyclohexane gradient (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C), Rt 0.68, MH+ 172 added reached −17° C. was added by peristaltic pump over 2 h the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigorous stirring to separate Brine (375 ml) was added the mixture stirred vigourously to separate The organic layer was dried (MgSO4) filtered evaporated to a brown oil (60 g) eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV) The product containing fractions were evaporated to dryness eluted with a ethyl acetate in cyclohexane gradient (0-40%) The clean, product containing fractions were evaporated to an off-white solid (15.41 g)

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry Tetrahydrofuran (THF) (150 ml) added. (2E)-2-butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. 1M Lithium tert-butoxide (655 ml, 655 mmol) was added by peristaltic pump over 2 hours, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was complete the mixture was stirred for 30 mins and brought to 0° C. Diethyl ether (450 ml) and 1M HCl (375 ml) were added and the mixture brought to 20° C. with vigorous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 ml) was added and the mixture stirred vigorously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (magnesium sulfate), filtered and evaporated to a brown oil (60 g). The mixture was loaded on to a 40+M Biotage silica column and eluted with DCM:ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a 1500 g Redisep Isco silica column and eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane. The clean, product containing fractions were evaporated to an off white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigorous stirring to separate Brine (375 ml) was added the mixture stirred vigorously to separate The organic layer was dried (magnesium sulfate) filtered evaporated to a brown oil (60 g) eluted with DCM:ethyl acetate (1:1 to 0:1, 10 CV) The product containing fractions were evaporated to dryness eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane The clean, product containing fractions were evaporated to an off white solid (15.41 g)

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCl) was charged to a 3 L Lara vessel and dry Tetrahydrofuran (THF) (150 ml) added. (2E)-2-butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under Nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. 1M Lithium tert-butoxide (655 ml, 655 mmol) was added by peristaltic pump over 2 hours, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was complete the mixture was stirred for 30 mins and brought to 0° C. Diethyl ether (450 ml) and 1M HCl (375 ml) were added and the mixture brought to 20° C. with vigourous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 ml) was added and the mixture stirred vigourously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (magnesium sulfate), filtered and evaporated to a brown oil (60 g). The mixture was loaded on to a 40+M Biotage silica column and eluted with DCM:ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a 1500 g Redisep Isco silica column and eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane. The clean, product containing fractions were evaporated to an off white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigourous stirring to separate Brine (375 ml) was added the mixture stirred vigourously to separate The organic layer was dried (magnesium sulfate) filtered evaporated to a brown oil (60 g) eluted with DCM:ethyl acetate (1:1 to 0:1, 10 CV) The product containing fractions were evaporated to dryness eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane The clean, product containing fractions were evaporated to an off white solid (15.41 g)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 50 ml of ethanol, 20.3 g (0.3 mole) of methylamine hydrochloride and 30.9 g (0.36 mole) of 37% formaldehyde aqueous solution were added and the mixture was warmed to 35°-40° C. Then, a solution prepared by dissolving 30.9 g (0.3 mole) of isopropyl carbamate in 150 ml of ethanol was added dropwise to the mixture with stirring maintaining the said temperature. After the dropwise addition of the solution, stirring was continued for 1 hour with heating and then the solvent was removed by distillation under reduced pressure. The residue was recrystallized from ethanol to give 42.7 g of isopropyl N-(methylaminomethyl)carbamate hydrochloride having a melting point of 163°-164° C. in yield of 77.8%. ##STR5## the mixture was warmed to 35°-40° C Then, a solution prepared was added dropwise to the mixture maintaining the said temperature After the dropwise addition of the solution stirring with heating the solvent was removed by distillation under reduced pressure The residue was recrystallized from ethanol

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry tetrahydrofuran (THF) (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. 1M Lithium tert-butoxide (655 mL, 655 mmol) was added by peristaltic pump over 2 hours, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was complete the mixture was stirred for 30 mins and brought to 0° C. Diethyl ether (450 ml) and 1M HCl (375 mL) were added and the mixture brought to 20° C. with vigorous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 mLI) was added and the mixture stirred vigorously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (magnesium sulfate), filtered and evaporated to a brown oil (60 g). The mixture was loaded on to a 40+M Biotage silica column and eluted with DCM:ethyl acetate (1:1 to 0:1, 10CV). The product containing fractions were evaporated to dryness and loaded on to a 1500 g Redisep Isco silica column and eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane. The clean, product containing fractions were evaporated to an off white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigorous stirring to separate Brine (375 mLI) was added the mixture stirred vigorously to separate The organic layer was dried (magnesium sulfate) filtered evaporated to a brown oil (60 g) eluted with DCM:ethyl acetate (1:1 to 0:1, 10CV) The product containing fractions were evaporated to dryness eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane The clean, product containing fractions were evaporated to an off white solid (15.41 g)

反応条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl carbamate (30 g, 291 mmol, available from TCl) was charged to a 3 L Lara vessel and dry tetrahydrofuran (THF) (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. Lithium tert-butoxide (1M, 655 mL, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 mL) were added and the mixture brought to 20° C. with vigourous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 mL) was added and the mixture stirred vigorously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The was applied to a silica column (40+M Biotage) and eluted with DCM/EtOAc (1:1 to 0:1, 10CV). The product containing fractions were evaporated to dryness and loaded on to a Redisep Isco silica column (1500 g) and eluted with a EtOAc in cyclohexane gradient (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C): Rt=0.68, MH+=172 added reached −17° C the reaction temperature between −10° C. and −18° C Once the addition brought to 0° C brought to 20° C. with vigourous stirring to separate Brine (375 mL) was added the mixture stirred vigorously to separate The organic layer was dried (MgSO4) filtered evaporated to a brown oil (60 g) eluted with DCM/EtOAc (1:1 to 0:1, 10CV) The product containing fractions were evaporated to dryness eluted with a EtOAc in cyclohexane gradient (0-40%) The clean, product containing fractions were evaporated to an off-white solid (15.41 g)