(2S)-2-[tert-butyl(dimethyl)silyl]oxypropanoyl chloride

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 60% sodium hydride (336 mg, 10 mmol) in mineral oil) in tetrahydrofuran (20 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (1.0 g, 9.0 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. The cooling bath was removed and the solution was allowed to warm to 25° C. to ensure complete anion generation. To the anion at 25° C. was added dropwise a solution of (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl chloride (2.23 g, 10 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. TLC indicated that the reaction was complete upon addition of the acid chloride (silica gel plates; hexane and ethyl acetate, 9:1). The solvent was removed by rotary evaporation affording a thick slug. The slug was dissolved in methylene chloride (75 mL) and washed with water (1×50 mL) and dried (MgSO4). Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length) using hexane and ethyl acetate (19:1) afforded 1.40 g (47%) of (5S)-N-((2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl)-5-ethenylpyrrolidin-2-one (9a) as clear liquid: 1H NMR (CDCl3) δ0.0300 (s,3 H), 0.0656 (s, 3 H), 0.877 (s, 9 H), 1.37 (d, J=6.5 Hz, 3 H), 1.82-1.88 (m, 1 H) 2.21 (p, J=10.7 Hz, 1 H), 2.34-2.47 (m, 1 H), 2.60 (p, J=9.8 Hz, 1 H), 4.88 (br, 1 H), 5.05-5.11 (m, 2 H), 5.36-5.38 (m, 1 H), 5.70-5.79 (m, 1 H); 13C NMR (CDCl3) δ174.86, 174.77, 135.5, 115.4, 66.8, 57.9, 31.6, 25.5, 24.4, 21.1, 18.1, -4.87, -5.16. The cooling bath was removed The solvent was removed by rotary evaporation affording a thick slug washed with water (1×50 mL) dried (MgSO4) Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 60% sodium hydride (336 mg, 10 mmol) in mineral oil) in tetrahydrofuran (20 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (1.0 g, 9.0 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. The cooling bath was removed and the solution was allowed to warm to 25° C. to ensure complete anion generation. To the anion at 25° C. was added dropwise a solution of (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl chloride (2.23 g, 10 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. TLC indicated that the reaction was complete upon addition of the acid chloride (silica gel plates; hexane and ethyl acetate, 9:1). The solvent was removed by rotary evaporation affording a thick slug. The slug was dissolved in methylene chloride (75 mL) and washed with water (1×50 mL) and dried (MgSO4). Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length) using hexane and ethyl acetate (19:1) afforded 1.40 g (47%) of (5S)-N-((2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl)-5-ethenylpyrrolidin-2-one (9a) as clear liquid: 1H NMR (CDCl3) δ0.0300 (s,3 H), 0.0656 (s, 3 H), 0.877 (s, 9 H), 1.37 (d, J=6.5 Hz, 3 H), 1.82-1.88 (m, 1 H) 2.21 (p, J=10.7 Hz, 1 H), 2.34-2.47 (m, 1 H), 2.60 (p, J=9.8 Hz, 1 H), 4.88 (br, 1 H), 5.05-5.11 (m, 2 H), 5.36-5.38 (m, 1 H), 5.70-5.79 (m, 1 H); 13C NMR (CDCl3) δ174.86, 174.77, 135.5, 115.4, 66.8, 57.9, 31.6, 25.5, 24.4, 21.1, 18.1, -4.87, -5.16. The cooling bath was removed The solvent was removed by rotary evaporation affording a thick slug washed with water (1×50 mL) dried (MgSO4) Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length)

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

実験手順: To a solution of 41.0 g (0.13 mol) of 2-(1,1-dimethylethyl)dimethylsilyl (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoate (7) and five drops of N,N-dimethylformamide in methylene chloride at 0° C. was added 70.8 mL (0.14 mol) of a 2.0M solution of oxalyl chloride in methylene chloride over a 30 minute period. The cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 18 hours. The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid. Purification by vacuum distillation afforded 25.6 g (88%) of (2S)-2-((1,1 -dimethylethyl)dimethylsilyloxy)propanoyl chloride (8) as a clear liquid: bp 42°-45° C. (1.5 mm Hg); 1H NMR (CDCl3) δ0.0920 (s, 3 H), 0.118 (s, 3 H), 0.909 (s, 9 H), 1.50 (d, J=6.7 Hz, 3 H), 4.49 (q, J=6.7 Hz, 1 H); 13C NMR (CDCl3) δ176.6, 76.0, 25.7, 25.6, 25.3, 20.9, 18.1, -1.57, -5.04, -5.28. The cooling bath was removed The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid Purification by vacuum distillation

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

実験手順: To a solution of 41.0 g (0.13 mol) of 2-(1,1-dimethylethyl)dimethylsilyl (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoate (7) and five drops of N,N-dimethylformamide in methylene chloride at 0° C. was added 70.8 mL (0.14 mol) of a 2.0M solution of oxalyl chloride in methylene chloride over a 30 minute period. The cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 18 hours. The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid. Purification by vacuum distillation afforded 25.6 g (88%) of (2S)-2-((1,1 -dimethylethyl)dimethylsilyloxy)propanoyl chloride (8) as a clear liquid: bp 42°-45° C. (1.5 mm Hg); 1H NMR (CDCl3) δ0.0920 (s, 3 H), 0.118 (s, 3 H), 0.909 (s, 9 H), 1.50 (d, J=6.7 Hz, 3 H), 4.49 (q, J=6.7 Hz, 1 H); 13C NMR (CDCl3) δ176.6, 76.0, 25.7, 25.6, 25.3, 20.9, 18.1, -1.57, -5.04, -5.28. The cooling bath was removed The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid Purification by vacuum distillation

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 60% sodium hydride (336 mg, 10 mmol) in mineral oil) in tetrahydrofuran (20 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (1.0 g, 9.0 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. The cooling bath was removed and the solution was allowed to warm to 25° C. to ensure complete anion generation. To the anion at 25° C. was added dropwise a solution of (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl chloride (2.23 g, 10 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. TLC indicated that the reaction was complete upon addition of the acid chloride (silica gel plates; hexane and ethyl acetate, 9:1). The solvent was removed by rotary evaporation affording a thick slug. The slug was dissolved in methylene chloride (75 mL) and washed with water (1×50 mL) and dried (MgSO4). Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length) using hexane and ethyl acetate (19:1) afforded 1.40 g (47%) of (5S)-N-((2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl)-5-ethenylpyrrolidin-2-one (9a) as clear liquid: 1H NMR (CDCl3) δ0.0300 (s,3 H), 0.0656 (s, 3 H), 0.877 (s, 9 H), 1.37 (d, J=6.5 Hz, 3 H), 1.82-1.88 (m, 1 H) 2.21 (p, J=10.7 Hz, 1 H), 2.34-2.47 (m, 1 H), 2.60 (p, J=9.8 Hz, 1 H), 4.88 (br, 1 H), 5.05-5.11 (m, 2 H), 5.36-5.38 (m, 1 H), 5.70-5.79 (m, 1 H); 13C NMR (CDCl3) δ174.86, 174.77, 135.5, 115.4, 66.8, 57.9, 31.6, 25.5, 24.4, 21.1, 18.1, -4.87, -5.16. The cooling bath was removed The solvent was removed by rotary evaporation affording a thick slug washed with water (1×50 mL) dried (MgSO4) Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length)

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

実験手順: To a solution of 41.0 g (0.13 mol) of 2-(1,1-dimethylethyl)dimethylsilyl (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoate (7) and five drops of N,N-dimethylformamide in methylene chloride at 0° C. was added 70.8 mL (0.14 mol) of a 2.0M solution of oxalyl chloride in methylene chloride over a 30 minute period. The cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 18 hours. The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid. Purification by vacuum distillation afforded 25.6 g (88%) of (2S)-2-((1,1 -dimethylethyl)dimethylsilyloxy)propanoyl chloride (8) as a clear liquid: bp 42°-45° C. (1.5 mm Hg); 1H NMR (CDCl3) δ0.0920 (s, 3 H), 0.118 (s, 3 H), 0.909 (s, 9 H), 1.50 (d, J=6.7 Hz, 3 H), 4.49 (q, J=6.7 Hz, 1 H); 13C NMR (CDCl3) δ176.6, 76.0, 25.7, 25.6, 25.3, 20.9, 18.1, -1.57, -5.04, -5.28. The cooling bath was removed The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid Purification by vacuum distillation

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 60% sodium hydride (336 mg, 10 mmol) in mineral oil) in tetrahydrofuran (20 mL) at 0° C. was added dropwise a solution of 5-vinylpyrrolidin-2-one (1.0 g, 9.0 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. The cooling bath was removed and the solution was allowed to warm to 25° C. to ensure complete anion generation. To the anion at 25° C. was added dropwise a solution of (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl chloride (2.23 g, 10 mmol) in tetrahydrofuran (10 mL) over a 5 minute period. TLC indicated that the reaction was complete upon addition of the acid chloride (silica gel plates; hexane and ethyl acetate, 9:1). The solvent was removed by rotary evaporation affording a thick slug. The slug was dissolved in methylene chloride (75 mL) and washed with water (1×50 mL) and dried (MgSO4). Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length) using hexane and ethyl acetate (19:1) afforded 1.40 g (47%) of (5S)-N-((2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoyl)-5-ethenylpyrrolidin-2-one (9a) as clear liquid: 1H NMR (CDCl3) δ0.0300 (s,3 H), 0.0656 (s, 3 H), 0.877 (s, 9 H), 1.37 (d, J=6.5 Hz, 3 H), 1.82-1.88 (m, 1 H) 2.21 (p, J=10.7 Hz, 1 H), 2.34-2.47 (m, 1 H), 2.60 (p, J=9.8 Hz, 1 H), 4.88 (br, 1 H), 5.05-5.11 (m, 2 H), 5.36-5.38 (m, 1 H), 5.70-5.79 (m, 1 H); 13C NMR (CDCl3) δ174.86, 174.77, 135.5, 115.4, 66.8, 57.9, 31.6, 25.5, 24.4, 21.1, 18.1, -4.87, -5.16. The cooling bath was removed The solvent was removed by rotary evaporation affording a thick slug washed with water (1×50 mL) dried (MgSO4) Concentration and purification by flash chromatography on silica gel (EM 60, 0.040-0.063 partical size, 230-400 Mesh, column size: 4.5 cm diameter×15 cm length)

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

実験手順: To a solution of 41.0 g (0.13 mol) of 2-(1,1-dimethylethyl)dimethylsilyl (2S)-2-((1,1-dimethylethyl)dimethylsilyloxy)propanoate (7) and five drops of N,N-dimethylformamide in methylene chloride at 0° C. was added 70.8 mL (0.14 mol) of a 2.0M solution of oxalyl chloride in methylene chloride over a 30 minute period. The cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 18 hours. The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid. Purification by vacuum distillation afforded 25.6 g (88%) of (2S)-2-((1,1 -dimethylethyl)dimethylsilyloxy)propanoyl chloride (8) as a clear liquid: bp 42°-45° C. (1.5 mm Hg); 1H NMR (CDCl3) δ0.0920 (s, 3 H), 0.118 (s, 3 H), 0.909 (s, 9 H), 1.50 (d, J=6.7 Hz, 3 H), 4.49 (q, J=6.7 Hz, 1 H); 13C NMR (CDCl3) δ176.6, 76.0, 25.7, 25.6, 25.3, 20.9, 18.1, -1.57, -5.04, -5.28. The cooling bath was removed The solvent and excess oxalyl chloride were removed by rotary evaporation resulting in a yellow liquid Purification by vacuum distillation