ethyl 2-carbamothioyl-2-methylacetate

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

実験手順: A mixture of diphenylphosphinodithioic acid (Alfa-Aesar) (7.48 g, 29.9 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 1.980 mL, 14.94 mmol) in isopropanol (80 mL) was heated under reflux for 8 h then stood at rt overnight. Reaction mixture was filtered and filtrate was diluted with EtOAc and washed with 1N NaOH, brine, and dried over Na2SO4. Crude was purified by chromatography on silica gel using a Hex/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a yellow oily solid. 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 8 h Reaction mixture was filtered filtrate was diluted with EtOAc washed with 1N NaOH, brine dried over Na2SO4 Crude was purified by chromatography on silica gel using a Hex/EtOAc gradient evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of Intermediate 103 (6.6 g, 40.9 mmol) and chloroacetone (FLUKA, 3.27 mL, 40.9 mmol) in DMF (50 mL) was stirred at 80° C. for 5 h. Reaction mixture was cooled to room temperature, treated with NaHCO3 (150 mL) and extracted with ethyl ether (2×200 mL). Organic layer was washed with brine, dried over Na2SO4 and evaporated to give title compound (7.57 g, 38.0 mmol, 93% yield) as yellow oil. 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.19 (s, 1H), 4.23-4.06 (m, 3H), 2.31 (s, 3H), 1.48 (d, 3H), 1.16 (t, 3H). [ES+MS] m/z 200 (MH+). It was subsequently observed that this compound undergoes autooxidation at the stereogenic centre to form ethyl 2-hydroxy-2-(4-methyl-1,3-thiazol-2-yl)propanoate. Once the presence of this compound had been observed, the compound was actively synthesised, hereinbelow described as Intermediate 106. Reaction mixture was cooled to room temperature extracted with ethyl ether (2×200 mL) Organic layer was washed with brine dried over Na2SO4 evaporated

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

実験手順: A mixture of diphenylphosphinodithioic acid (ALFAAESAR, 37.4 g, 149 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 9.90 mL, 74.7 mmol) in isopropanol (350 mL) was heated under reflux for 5 h. TLC (Hex:EtOAc 7:3) showed reaction had gone to completion. Reaction mixture was allowed to cool and was placed in the fridge overnight. Reaction mixture was filtered off and washed with isopropanol. Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL). Phases were separated and organic phase was washed with water (300 mL), brine (300 mL), dried over sodium sulfate and concentrated to dryness. Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a white solid (6.6 g, 40.9 mmol, 54.8% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 5 h reaction Reaction mixture to cool was placed in the fridge overnight Reaction mixture was filtered off washed with isopropanol Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL) Phases were separated organic phase was washed with water (300 mL), brine (300 mL) dried over sodium sulfate concentrated to dryness Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient evaporated

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

実験手順: A mixture of diphenylphosphinodithioic acid (Alfa-Aesar) (7.48 g, 29.9 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 1.980 mL, 14.94 mmol) in isopropanol (80 mL) was heated under reflux for 8 h then stood at rt overnight. Reaction mixture was filtered and filtrate was diluted with EtOAc and washed with 1N NaOH, brine, and dried over Na2SO4. Crude was purified by chromatography on silica gel using a Hex/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a yellow oily solid. 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 8 h Reaction mixture was filtered filtrate was diluted with EtOAc washed with 1N NaOH, brine dried over Na2SO4 Crude was purified by chromatography on silica gel using a Hex/EtOAc gradient evaporated

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

実験手順: A mixture of diphenylphosphinodithioic acid (Alfa-Aesar) (7.48 g, 29.9 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 1.980 mL, 14.94 mmol) in isopropanol (80 mL) was heated under reflux for 8 h then stood at rt overnight. Reaction mixture was filtered and filtrate was diluted with EtOAc and washed with 1N NaOH, brine, and dried over Na2SO4. Crude was purified by chromatography on silica gel using a Hex/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a yellow oily solid. 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 8 h Reaction mixture was filtered filtrate was diluted with EtOAc washed with 1N NaOH, brine dried over Na2SO4 Crude was purified by chromatography on silica gel using a Hex/EtOAc gradient evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of Intermediate 103 (6.6 g, 40.9 mmol) and chloroacetone (FLUKA, 3.27 mL, 40.9 mmol) in DMF (50 mL) was stirred at 80° C. for 5 h. Reaction mixture was cooled to room temperature, treated with NaHCO3 (150 mL) and extracted with ethyl ether (2×200 mL). Organic layer was washed with brine, dried over Na2SO4 and evaporated to give title compound (7.57 g, 38.0 mmol, 93% yield) as yellow oil. 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.19 (s, 1H), 4.23-4.06 (m, 3H), 2.31 (s, 3H), 1.48 (d, 3H), 1.16 (t, 3H). [ES+MS] m/z 200 (MH+). It was subsequently observed that this compound undergoes autooxidation at the stereogenic centre to form ethyl 2-hydroxy-2-(4-methyl-1,3-thiazol-2-yl)propanoate. Once the presence of this compound had been observed, the compound was actively synthesised, hereinbelow described as Intermediate 106. Reaction mixture was cooled to room temperature extracted with ethyl ether (2×200 mL) Organic layer was washed with brine dried over Na2SO4 evaporated

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

実験手順: A mixture of diphenylphosphinodithioic acid (ALFAAESAR, 37.4 g, 149 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 9.90 mL, 74.7 mmol) in isopropanol (350 mL) was heated under reflux for 5 h. TLC (Hex:EtOAc 7:3) showed reaction had gone to completion. Reaction mixture was allowed to cool and was placed in the fridge overnight. Reaction mixture was filtered off and washed with isopropanol. Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL). Phases were separated and organic phase was washed with water (300 mL), brine (300 mL), dried over sodium sulfate and concentrated to dryness. Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a white solid (6.6 g, 40.9 mmol, 54.8% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 5 h reaction Reaction mixture to cool was placed in the fridge overnight Reaction mixture was filtered off washed with isopropanol Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL) Phases were separated organic phase was washed with water (300 mL), brine (300 mL) dried over sodium sulfate concentrated to dryness Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient evaporated

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

実験手順: A mixture of diphenylphosphinodithioic acid (ALFAAESAR, 37.4 g, 149 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 9.90 mL, 74.7 mmol) in isopropanol (350 mL) was heated under reflux for 5 h. TLC (Hex:EtOAc 7:3) showed reaction had gone to completion. Reaction mixture was allowed to cool and was placed in the fridge overnight. Reaction mixture was filtered off and washed with isopropanol. Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL). Phases were separated and organic phase was washed with water (300 mL), brine (300 mL), dried over sodium sulfate and concentrated to dryness. Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a white solid (6.6 g, 40.9 mmol, 54.8% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 5 h reaction Reaction mixture to cool was placed in the fridge overnight Reaction mixture was filtered off washed with isopropanol Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL) Phases were separated organic phase was washed with water (300 mL), brine (300 mL) dried over sodium sulfate concentrated to dryness Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient evaporated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of Intermediate 103 (6.6 g, 40.9 mmol) and chloroacetone (FLUKA, 3.27 mL, 40.9 mmol) in DMF (50 mL) was stirred at 80° C. for 5 h. Reaction mixture was cooled to room temperature, treated with NaHCO3 (150 mL) and extracted with ethyl ether (2×200 mL). Organic layer was washed with brine, dried over Na2SO4 and evaporated to give title compound (7.57 g, 38.0 mmol, 93% yield) as yellow oil. 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.19 (s, 1H), 4.23-4.06 (m, 3H), 2.31 (s, 3H), 1.48 (d, 3H), 1.16 (t, 3H). [ES+MS] m/z 200 (MH+). It was subsequently observed that this compound undergoes autooxidation at the stereogenic centre to form ethyl 2-hydroxy-2-(4-methyl-1,3-thiazol-2-yl)propanoate. Once the presence of this compound had been observed, the compound was actively synthesised, hereinbelow described as Intermediate 106. Reaction mixture was cooled to room temperature extracted with ethyl ether (2×200 mL) Organic layer was washed with brine dried over Na2SO4 evaporated

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

実験手順: A mixture of diphenylphosphinodithioic acid (ALFAAESAR, 37.4 g, 149 mmol) and 2-cyanopropionic acid ethyl ester (ABCR, 9.90 mL, 74.7 mmol) in isopropanol (350 mL) was heated under reflux for 5 h. TLC (Hex:EtOAc 7:3) showed reaction had gone to completion. Reaction mixture was allowed to cool and was placed in the fridge overnight. Reaction mixture was filtered off and washed with isopropanol. Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL). Phases were separated and organic phase was washed with water (300 mL), brine (300 mL), dried over sodium sulfate and concentrated to dryness. Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient. Appropriate fractions were combined and evaporated to yield title compound as a white solid (6.6 g, 40.9 mmol, 54.8% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.60 (s, 1H), 9.40 (s, 1H), 4.05 (q, 2H), 3.74 (q, 1H), 1.29 (d, 3H), 1.15 (t, 3H). [ES+MS] m/z 162 (MH+). was heated under reflux for 5 h reaction Reaction mixture to cool was placed in the fridge overnight Reaction mixture was filtered off washed with isopropanol Residue was partitioned between ethyl acetate (250 mL) and 1N NaOH (250 mL) Phases were separated organic phase was washed with water (300 mL), brine (300 mL) dried over sodium sulfate concentrated to dryness Crude was purified by chromatography on silica gel using a hexane/EtOAc gradient evaporated