methyl (3S)-4-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.0 g, 30.0 mmol) in acetone (90 mL), there was added 2,2-dimethoxypropane (37 mL, 300 mmol) followed by BF3.Et2O (0.11 mL, 0.9 mmol). The resulting solution was stirred at rt overnight. Solvents were removed under vacuum, and the residue was redissolved in ether (100 mL), washed with sat'd NaHCO3 (20 mL). Upon concentrating under vacuum, the residue was purified by flash column chromatography to give (S)-tert-butyl 4-(2-methoxy-2-oxoethyl)-2,2-dimethyloxazolidine-3-carboxylate (7.51 g, 92%). MS m/z 296 (M+Na+). Solvents were removed under vacuum the residue was redissolved in ether (100 mL) washed with sat'd NaHCO3 (20 mL) Upon concentrating under vacuum the residue was purified by flash column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.0 g, 30.0 mmol) in acetone (90 mL), there was added 2,2-dimethoxypropane (37 mL, 300 mmol) followed by BF3.Et2O (0.11 mL, 0.9 mmol). The resulting solution was stirred at rt overnight. Solvents were removed under vacuum, and the residue was redissolved in ether (100 mL), washed with sat'd NaHCO3 (20 mL). Upon concentrating under vacuum, the residue was purified by flash column chromatography to give (S)-tert-butyl 4-(2-methoxy-2-oxoethyl)-2,2-dimethyloxazolidine-3-carboxylate (7.51 g, 92%). MS m/z 296 (M+Na+). Solvents were removed under vacuum the residue was redissolved in ether (100 mL) washed with sat'd NaHCO3 (20 mL) Upon concentrating under vacuum the residue was purified by flash column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-4-methoxy-4-oxobutanoic acid (9.0 g, 35.7 mmol) in THF (180 mL) at −10° C. was added N-methylmorpholine (3.9 mL, 35.7 mmol) followed by ethyl chloroformate (3.91 g, 35.7 mmol). After 10 min, the mixture was transferred slowly to a mixture of NaBH4 (2.7 g, 71.4 mmol) and ice water (900 mL). The resulting solution was stirred for 1 h, NaHCO3 (˜20 g) was added, and the organic layer was separated. The aqueous layer was extracted with EtOAc (4×200 mL). The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL), dried over Na2SO4, and concentrated to give (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.06 g, 85%) as an oil. MS m/z 234 (M+H+). the organic layer was separated The aqueous layer was extracted with EtOAc (4×200 mL) The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL) dried over Na2SO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-4-methoxy-4-oxobutanoic acid (9.0 g, 35.7 mmol) in THF (180 mL) at −10° C. was added N-methylmorpholine (3.9 mL, 35.7 mmol) followed by ethyl chloroformate (3.91 g, 35.7 mmol). After 10 min, the mixture was transferred slowly to a mixture of NaBH4 (2.7 g, 71.4 mmol) and ice water (900 mL). The resulting solution was stirred for 1 h, NaHCO3 (˜20 g) was added, and the organic layer was separated. The aqueous layer was extracted with EtOAc (4×200 mL). The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL), dried over Na2SO4, and concentrated to give (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.06 g, 85%) as an oil. MS m/z 234 (M+H+). the organic layer was separated The aqueous layer was extracted with EtOAc (4×200 mL) The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL) dried over Na2SO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.0 g, 30.0 mmol) in acetone (90 mL), there was added 2,2-dimethoxypropane (37 mL, 300 mmol) followed by BF3.Et2O (0.11 mL, 0.9 mmol). The resulting solution was stirred at rt overnight. Solvents were removed under vacuum, and the residue was redissolved in ether (100 mL), washed with sat'd NaHCO3 (20 mL). Upon concentrating under vacuum, the residue was purified by flash column chromatography to give (S)-tert-butyl 4-(2-methoxy-2-oxoethyl)-2,2-dimethyloxazolidine-3-carboxylate (7.51 g, 92%). MS m/z 296 (M+Na+). Solvents were removed under vacuum the residue was redissolved in ether (100 mL) washed with sat'd NaHCO3 (20 mL) Upon concentrating under vacuum the residue was purified by flash column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-4-methoxy-4-oxobutanoic acid (9.0 g, 35.7 mmol) in THF (180 mL) at −10° C. was added N-methylmorpholine (3.9 mL, 35.7 mmol) followed by ethyl chloroformate (3.91 g, 35.7 mmol). After 10 min, the mixture was transferred slowly to a mixture of NaBH4 (2.7 g, 71.4 mmol) and ice water (900 mL). The resulting solution was stirred for 1 h, NaHCO3 (˜20 g) was added, and the organic layer was separated. The aqueous layer was extracted with EtOAc (4×200 mL). The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL), dried over Na2SO4, and concentrated to give (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.06 g, 85%) as an oil. MS m/z 234 (M+H+). the organic layer was separated The aqueous layer was extracted with EtOAc (4×200 mL) The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL) dried over Na2SO4 concentrated