tert-butyl N,N-dimethylcarbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl dimethylcarbamate (57.8 g) in N,N,N′,N′-tetramethylethylenediamine (70 ml) and MTBE (485 g) was added sec-butyl lithium (1.4 M in cyclohexane, 300 ml) over 0.5 h while maintaining the temperature below −65° C. The mixture was stirred at −65° C. for 0.5 h, then magnesium bromide diethyl etherate (111.07 g) was added with an exotherm to −60° C. The resultant slurry was allowed to warm to −11° C. over 0.5 h then cooled to −72° C. The slurry was cannulated into a −72° C. solution of N-methoxy-N-methylpyrimidine-2-carboxamide (27.2 g) in methylene chloride (400 ml) with an exotherm to −60° C. and rinsed in with MTBE (25 ml). The mixture was warmed to 0° C. over 45 min then cooled to −27° C. Acetone (30.5 ml) was added. The mixture was cooled to −29° C., then a solution of acetic acid (63.7 g) in water (303 ml) was added with an exotherm to 11° C. The mixture was warmed to 20° C. and the phases separated. The organic layer was washed with saturated aq. sodium bicarbonate (250 ml) and the aqueous phases serial back extracted with MTBE (350 ml). The combined organics were dried (MgSO4) and concentrated in vacuo to a net weight of 85 g. Toluene (200 ml) was added and the mixture concentrated to 128 g net weight. Branched octanes (205 g) was added to the cloud point, the mixture seeded and the product allowed to precipitate for 15 minutes with stirring. The slurry was cooled to −19° C. and the precipitate collected by vacuum filtration, washed with branched octanes (82 g) and dried in a nitrogen stream to afford 29.27 g of the title compound as a solid. Physical characteristics are as follows: 1H NMR (400 MHz, CDCl3) δ 1.38, 1.49, 3.00, 4.83, 4.92, 7.50, 8.94; 13C NMR (100 MHz, CDCl3) δ 28.11, 28.30, 35.57, 35.71, 56.11, 56.61, 79.96, 123.25, 123.36, 157.56, 157.65. while maintaining the temperature below −65° C to warm to −11° C. over 0.5 h then cooled to −72° C was cannulated into a −72° C. to −60° C. rinsed in with MTBE (25 ml) The mixture was warmed to 0° C. over 45 min then cooled to −27° C Acetone (30.5 ml) was added The mixture was cooled to −29° C. a solution of acetic acid (63.7 g) in water (303 ml) was added with an exotherm to 11° C The mixture was warmed to 20° C. the phases separated The organic layer was washed with saturated aq. sodium bicarbonate (250 ml) the aqueous phases serial back extracted with MTBE (350 ml) The combined organics were dried (MgSO4) concentrated in vacuo to a net weight of 85 g Toluene (200 ml) was added the mixture concentrated to 128 g net weight Branched octanes (205 g) was added to the cloud point to precipitate for 15 minutes with stirring The slurry was cooled to −19° C. the precipitate collected by vacuum filtration washed with branched octanes (82 g) dried in a nitrogen stream

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

実験手順: To a solution of tert-butyl dimethylcarbamate (1.8 g, 0.012 mol) and tetramethylethylenediamine (2.6 g, 0.022 mol) in THF (anhydrous, 30 mL) was added sec-butyllithium (1.4 M in cyclohexane, 11 mL, 0.015 mmol) at −78° C. The mixture was stirred at that temperature for 30 minutes before a solution of 6-methoxy-3-pyridinecarboxaldehyde (J.Org.Chem. 55; 1; 1990; 69-73)(1.4 g, 0.01 mol, in 5 mL of dry THF) was introduced. The reaction mixture was stirred for 30 minutes, warmed to room temperature and stirred for 3 hours. Saturated ammonium chloride aqueous solution (20 mL) was added to quench the reaction after the reaction mixture was cooled to −78° C. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with brine and dried over sodium sulfate and concentrated. The residue was purified with a silica gel column to give the title compound (1.2 g) as a white solid. was introduced stirred for 3 hours to quench the reaction after the reaction mixture was cooled to −78° C The organic phase was separated the aqueous phase was extracted with dichloromethane washed with brine dried over sodium sulfate concentrated The residue was purified with a silica gel column

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

実験手順: To a solution of tert-butyl dimethylcarbamate (350 mg, 2.4 mmol) and tetramethylethylenediamine (511 mg, 4.4 mmol) in THF (anhydrous, 10 mL) was added sec-butyllithium (1.4 M in cyclohexane, 2.2 mL, 3.1 mmol) at −78° C. The mixture was stirred at that temperature for 1 hour before 4-[(dimethylamino)methyl]benzaldehyde (J.Heterocycl.Chem.; 26; 1989; 1325-1330)(280 mg, 1.7 mmol) was introduced. The reaction mixture was stirred for 2 hours, warmed to room temperature and stirred for 1 hour. Saturated ammonium chloride aqueous solution (10 mL) was added to quench the reaction after the reaction mixture was cooled to −78° C. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with brine and dried over sodium sulfate and concentrated. The residue was purified with a silica gel column to give the title compound (0.40 g) as a white solid. was introduced stirred for 1 hour to quench the reaction after the reaction mixture was cooled to −78° C The organic phase was separated the aqueous phase was extracted with dichloromethane washed with brine dried over sodium sulfate concentrated The residue was purified with a silica gel column

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl dimethylcarbamate (57.8 g) in N,N,N′,N′-tetramethylethylenediamine (70 ml) and MTBE (485 g) was added sec-butyl lithium (1.4 M in cyclohexane, 300 ml) over 0.5 h while maintaining the temperature below −65° C. The mixture was stirred at −65° C. for 0.5 h, then magnesium bromide diethyl etherate (111.07 g) was added with an exotherm to −60° C. The resultant slurry was allowed to warm to −11° C. over 0.5 h then cooled to −72° C. The slurry was cannulated into a −72° C. solution of N-methoxy-N-methylpyrimidine-2-carboxamide (27.2 g) in methylene chloride (400 ml) with an exotherm to −60° C. and rinsed in with MTBE (25 ml). The mixture was warmed to 0° C. over 45 min then cooled to −27° C. Acetone (30.5 ml) was added. The mixture was cooled to −29° C., then a solution of acetic acid (63.7 g) in water (303 ml) was added with an exotherm to 11° C. The mixture was warmed to 20° C. and the phases separated. The organic layer was washed with saturated aq. sodium bicarbonate (250 ml) and the aqueous phases serial back extracted with MTBE (350 ml). The combined organics were dried (MgSO4) and concentrated in vacuo to a net weight of 85 g. Toluene (200 ml) was added and the mixture concentrated to 128 g net weight. Branched octanes (205 g) was added to the cloud point, the mixture seeded and the product allowed to precipitate for 15 minutes with stirring. The slurry was cooled to −19° C. and the precipitate collected by vacuum filtration, washed with branched octanes (82 g) and dried in a nitrogen stream to afford 29.27 g of the title compound as a solid. Physical characteristics are as follows: 1H NMR (400 MHz, CDCl3) δ 1.38, 1.49, 3.00, 4.83, 4.92, 7.50, 8.94; 13C NMR (100 MHz, CDCl3) δ 28.11, 28.30, 35.57, 35.71, 56.11, 56.61, 79.96, 123.25, 123.36, 157.56, 157.65. while maintaining the temperature below −65° C to warm to −11° C. over 0.5 h then cooled to −72° C was cannulated into a −72° C. to −60° C. rinsed in with MTBE (25 ml) The mixture was warmed to 0° C. over 45 min then cooled to −27° C Acetone (30.5 ml) was added The mixture was cooled to −29° C. a solution of acetic acid (63.7 g) in water (303 ml) was added with an exotherm to 11° C The mixture was warmed to 20° C. the phases separated The organic layer was washed with saturated aq. sodium bicarbonate (250 ml) the aqueous phases serial back extracted with MTBE (350 ml) The combined organics were dried (MgSO4) concentrated in vacuo to a net weight of 85 g Toluene (200 ml) was added the mixture concentrated to 128 g net weight Branched octanes (205 g) was added to the cloud point to precipitate for 15 minutes with stirring The slurry was cooled to −19° C. the precipitate collected by vacuum filtration washed with branched octanes (82 g) dried in a nitrogen stream

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

実験手順: To a solution of tert-butyl dimethylcarbamate (1.8 g, 0.012 mol) and tetramethylethylenediamine (2.6 g, 0.022 mol) in THF (anhydrous, 30 mL) was added sec-butyllithium (1.4 M in cyclohexane, 11 mL, 0.015 mmol) at −78° C. The mixture was stirred at that temperature for 30 minutes before a solution of 6-methoxy-3-pyridinecarboxaldehyde (J.Org.Chem. 55; 1; 1990; 69-73)(1.4 g, 0.01 mol, in 5 mL of dry THF) was introduced. The reaction mixture was stirred for 30 minutes, warmed to room temperature and stirred for 3 hours. Saturated ammonium chloride aqueous solution (20 mL) was added to quench the reaction after the reaction mixture was cooled to −78° C. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with brine and dried over sodium sulfate and concentrated. The residue was purified with a silica gel column to give the title compound (1.2 g) as a white solid. was introduced stirred for 3 hours to quench the reaction after the reaction mixture was cooled to −78° C The organic phase was separated the aqueous phase was extracted with dichloromethane washed with brine dried over sodium sulfate concentrated The residue was purified with a silica gel column

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

実験手順: To a solution of tert-butyl dimethylcarbamate (350 mg, 2.4 mmol) and tetramethylethylenediamine (511 mg, 4.4 mmol) in THF (anhydrous, 10 mL) was added sec-butyllithium (1.4 M in cyclohexane, 2.2 mL, 3.1 mmol) at −78° C. The mixture was stirred at that temperature for 1 hour before 4-[(dimethylamino)methyl]benzaldehyde (J.Heterocycl.Chem.; 26; 1989; 1325-1330)(280 mg, 1.7 mmol) was introduced. The reaction mixture was stirred for 2 hours, warmed to room temperature and stirred for 1 hour. Saturated ammonium chloride aqueous solution (10 mL) was added to quench the reaction after the reaction mixture was cooled to −78° C. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with brine and dried over sodium sulfate and concentrated. The residue was purified with a silica gel column to give the title compound (0.40 g) as a white solid. was introduced stirred for 1 hour to quench the reaction after the reaction mixture was cooled to −78° C The organic phase was separated the aqueous phase was extracted with dichloromethane washed with brine dried over sodium sulfate concentrated The residue was purified with a silica gel column

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl dimethylcarbamate (57.8 g) in N,N,N′,N′-tetramethylethylenediamine (70 ml) and MTBE (485 g) was added sec-butyl lithium (1.4 M in cyclohexane, 300 ml) over 0.5 h while maintaining the temperature below −65° C. The mixture was stirred at −65° C. for 0.5 h, then magnesium bromide diethyl etherate (111.07 g) was added with an exotherm to −60° C. The resultant slurry was allowed to warm to −11° C. over 0.5 h then cooled to −72° C. The slurry was cannulated into a −72° C. solution of N-methoxy-N-methylpyrimidine-2-carboxamide (27.2 g) in methylene chloride (400 ml) with an exotherm to −60° C. and rinsed in with MTBE (25 ml). The mixture was warmed to 0° C. over 45 min then cooled to −27° C. Acetone (30.5 ml) was added. The mixture was cooled to −29° C., then a solution of acetic acid (63.7 g) in water (303 ml) was added with an exotherm to 11° C. The mixture was warmed to 20° C. and the phases separated. The organic layer was washed with saturated aq. sodium bicarbonate (250 ml) and the aqueous phases serial back extracted with MTBE (350 ml). The combined organics were dried (MgSO4) and concentrated in vacuo to a net weight of 85 g. Toluene (200 ml) was added and the mixture concentrated to 128 g net weight. Branched octanes (205 g) was added to the cloud point, the mixture seeded and the product allowed to precipitate for 15 minutes with stirring. The slurry was cooled to −19° C. and the precipitate collected by vacuum filtration, washed with branched octanes (82 g) and dried in a nitrogen stream to afford 29.27 g of the title compound as a solid. Physical characteristics are as follows: 1H NMR (400 MHz, CDCl3) δ 1.38, 1.49, 3.00, 4.83, 4.92, 7.50, 8.94; 13C NMR (100 MHz, CDCl3) δ 28.11, 28.30, 35.57, 35.71, 56.11, 56.61, 79.96, 123.25, 123.36, 157.56, 157.65. while maintaining the temperature below −65° C to warm to −11° C. over 0.5 h then cooled to −72° C was cannulated into a −72° C. to −60° C. rinsed in with MTBE (25 ml) The mixture was warmed to 0° C. over 45 min then cooled to −27° C Acetone (30.5 ml) was added The mixture was cooled to −29° C. a solution of acetic acid (63.7 g) in water (303 ml) was added with an exotherm to 11° C The mixture was warmed to 20° C. the phases separated The organic layer was washed with saturated aq. sodium bicarbonate (250 ml) the aqueous phases serial back extracted with MTBE (350 ml) The combined organics were dried (MgSO4) concentrated in vacuo to a net weight of 85 g Toluene (200 ml) was added the mixture concentrated to 128 g net weight Branched octanes (205 g) was added to the cloud point to precipitate for 15 minutes with stirring The slurry was cooled to −19° C. the precipitate collected by vacuum filtration washed with branched octanes (82 g) dried in a nitrogen stream

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

実験手順: To a solution of tert-butyl dimethylcarbamate (1.8 g, 0.012 mol) and tetramethylethylenediamine (2.6 g, 0.022 mol) in THF (anhydrous, 30 mL) was added sec-butyllithium (1.4 M in cyclohexane, 11 mL, 0.015 mmol) at −78° C. The mixture was stirred at that temperature for 30 minutes before a solution of 6-methoxy-3-pyridinecarboxaldehyde (J.Org.Chem. 55; 1; 1990; 69-73)(1.4 g, 0.01 mol, in 5 mL of dry THF) was introduced. The reaction mixture was stirred for 30 minutes, warmed to room temperature and stirred for 3 hours. Saturated ammonium chloride aqueous solution (20 mL) was added to quench the reaction after the reaction mixture was cooled to −78° C. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with brine and dried over sodium sulfate and concentrated. The residue was purified with a silica gel column to give the title compound (1.2 g) as a white solid. was introduced stirred for 3 hours to quench the reaction after the reaction mixture was cooled to −78° C The organic phase was separated the aqueous phase was extracted with dichloromethane washed with brine dried over sodium sulfate concentrated The residue was purified with a silica gel column

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

実験手順: To a solution of tert-butyl dimethylcarbamate (350 mg, 2.4 mmol) and tetramethylethylenediamine (511 mg, 4.4 mmol) in THF (anhydrous, 10 mL) was added sec-butyllithium (1.4 M in cyclohexane, 2.2 mL, 3.1 mmol) at −78° C. The mixture was stirred at that temperature for 1 hour before 4-[(dimethylamino)methyl]benzaldehyde (J.Heterocycl.Chem.; 26; 1989; 1325-1330)(280 mg, 1.7 mmol) was introduced. The reaction mixture was stirred for 2 hours, warmed to room temperature and stirred for 1 hour. Saturated ammonium chloride aqueous solution (10 mL) was added to quench the reaction after the reaction mixture was cooled to −78° C. The organic phase was separated and the aqueous phase was extracted with dichloromethane. The organic phases were combined, washed with brine and dried over sodium sulfate and concentrated. The residue was purified with a silica gel column to give the title compound (0.40 g) as a white solid. was introduced stirred for 1 hour to quench the reaction after the reaction mixture was cooled to −78° C The organic phase was separated the aqueous phase was extracted with dichloromethane washed with brine dried over sodium sulfate concentrated The residue was purified with a silica gel column