dimethyl (2R)-2-[[(4-fluorophenyl)sulfonyl]amino]-butanedioate

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

Procedure: To a suspension of D-aspartic acid dimethyl ester hydrochloride (36.0 g, 182 mmol) in THF (360 mL) was added 4-fluorobenzenesulfonyl chloride (39.0 g, 200 mmol, 1.1 equiv.). To the previous mixture at 0° C. was added dropwise triethylamine (60.8 g, 601 mmol, 3.3 equiv.). After a period of 18 h at room temperature, the reaction mixture was filtered and the solid washed with methyl tert-butyl ether (30 mL). The filtrate was evaporated followed by the addition of methyl tert-butyl ether (300 mL). To the resulting mixture was added 100 mL of HCl 1 M. The organic phase was separated and sequentially washed with water, half-saturated sodium bicarbonate, HCl 0.5 M and half-saturated sodium chloride. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure to give 50 g of the title compound as an oil. the reaction mixture was filtered the solid washed with methyl tert-butyl ether (30 mL) The filtrate was evaporated followed by the addition of methyl tert-butyl ether (300 mL) To the resulting mixture was added 100 mL of HCl 1 M The organic phase was separated sequentially washed with water, half-saturated sodium bicarbonate, HCl 0.5 M and half-saturated sodium chloride The organic phase was dried over magnesium sulfate filtered evaporated under reduced pressure

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

Procedure: To a cooled (0° C.) solution of dimethyl (2R)-2-{[(4-fluorophenyl)sulfonyl]-amino}succinate (1 equiv.) from step 1 in EtOH (10 mL/g) was added NaBH4 (5 equiv.) in 3 portions and the reaction was stirred overnight at rt. The reaction was quenched with brine (5 mL/g) and filtered. The solid was suspended in EtOAc (10 mL/g). The mother liquor was concentrated in vacuo and then saturated with NaCl. The EtOAc suspension was then filtered. The reaction was quenched with brine (5 mL/g) filtered The mother liquor was concentrated in vacuo The EtOAc suspension was then filtered

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

Procedure: To a suspension of D-aspartic acid dimethyl ester hydrochloride (36.0 g, 182 mmol) in THF (360 mL) was added 4-fluorobenzenesulfonyl chloride (39.0 g, 200 mmol, 1.1 equiv.). To the previous mixture at 0° C. was added dropwise triethylamine (60.8 g, 601 mmol, 3.3 equiv.). After a period of 18 h at room temperature, the reaction mixture was filtered and the solid washed with methyl tert-butyl ether (30 mL). The filtrate was evaporated followed by the addition of methyl tert-butyl ether (300 mL). To the resulting mixture was added 100 mL of HCl 1 M. The organic phase was separated and sequentially washed with water, half-saturated sodium bicarbonate, HCl 0.5 M and half-saturated sodium chloride. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure to give 50 g of the title compound as an oil. the reaction mixture was filtered the solid washed with methyl tert-butyl ether (30 mL) The filtrate was evaporated followed by the addition of methyl tert-butyl ether (300 mL) To the resulting mixture was added 100 mL of HCl 1 M The organic phase was separated sequentially washed with water, half-saturated sodium bicarbonate, HCl 0.5 M and half-saturated sodium chloride The organic phase was dried over magnesium sulfate filtered evaporated under reduced pressure

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

Procedure: To a cooled (0° C.) solution of dimethyl (2R)-2-{[(4-fluorophenyl)sulfonyl]-amino}succinate (1 equiv.) from step 1 in EtOH (10 mL/g) was added NaBH4 (5 equiv.) in 3 portions and the reaction was stirred overnight at rt. The reaction was quenched with brine (5 mL/g) and filtered. The solid was suspended in EtOAc (10 mL/g). The mother liquor was concentrated in vacuo and then saturated with NaCl. The EtOAc suspension was then filtered. The reaction was quenched with brine (5 mL/g) filtered The mother liquor was concentrated in vacuo The EtOAc suspension was then filtered