dimethyl (2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2.61 g (10 m mol) of dimethyl (R)-N-tert-butoxycarbonylaspartate in 10 ml of tetrahydrofuran was added dropwise to a lithium diisopropylamide solution [prepared from 4.62 ml (33 m mol) of diisopropylamine and 21 ml (33 m mol) of butyllithium-hexane solution, in 30 ml of tetrahydrofuran]at -78° C. in a stream of nitrogen, and the mixture was stirred for 10 minutes at -78° C. Then, a solution of 2.76 g (20 m mol) of isobutyrylimidazole in 15 ml of tetrahydrofuran was added dropwise to the reaction mixture, and the mixture was stirred for 10 minutes at -78° C. and further in a dry ice-acetone bath of -40° C. The mixture was further stirred until the temperature reached -20° C., to which a saturated ammonium chloride solution was added and stirred at room temperature. The reaction mixture was diluted with water and and extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over sodium sulfate and distilled. The residue was subjected to a silica gel column (2.5×40 cm) chromatography (ethyl acetate:hexane=1:3→1:2) to obtain 2.07 g (62%) of dimethyl (R)-N-tert-butoxycarbonyl-3-isobutyrylaspartate as colorless oil. the mixture was stirred for 10 minutes at -78° C. and further in a dry ice-acetone bath of -40° C The mixture was further stirred until the temperature reached -20° C., to which was added stirred at room temperature extracted with ethyl acetate The organic layer was washed with a saturated saline solution dried over sodium sulfate distilled

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

Procedure: A solution of 2.61 g (10 m mol) of dimethyl (R)-N-tert-butoxycarbonylaspartate in 10 ml of tetrahydrofuran was added dropwise to a lithium isopropylamide solution [prepared from 4.62 ml (33 m mol) of diisopropylamine and 21 ml (33 m mol) of butyllithium hexane solution, in 30 ml of tetrahydrofuran]at -78° C. in a stream of nitrogen. The mixture was stirred for 10 minutes and a solution of 2.48 g (20 m mol) of propionylimidazole in 15 ml of tetrahydrofuran was added dropwise. The reaction mixture was stirred for 10 minutes at -78° C. and further stirred in a dry ice-acetone bath of -40° C. Stirring was continued until the temperature of the mixture reached -20° C. Then a saturated ammonium chloride aqueous solution was added and the mixture was stirred at room temperature. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, dried over anhydrous sodium sulfate and distilled under reduced pressure. The residue was subjected to a silica gel column (2.5×40 cm) chromatography (ethyl acetate:hexane=1:3→1:2) to obtain 2.93 g (92%) of dimethyl (R)-N-tert-butoxycarbonyl-3-propionylaspartate as colorless oil. The reaction mixture was stirred for 10 minutes at -78° C. further stirred in a dry ice-acetone bath of -40° C Stirring reached -20° C the mixture was stirred at room temperature extracted with ethyl acetate The organic layer was washed with a saturated saline solution dried over anhydrous sodium sulfate distilled under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of lithium diisopropylamide (30.8%, 10.5 ml, 22 m mol) in hexane was added to a solution of dimethyl (R)-N-tert-butoxycarbonylaspartate (2.61 g, 10 m mol) in tetrahydrofuran (50 ml) at -78° C. in a stream of nitrogen and the mixture was stirred for 10 minutes at -78° C. After stirring for 20 minutes at -40° C., the reaction mixture was again cooled to -78° C., to which a solution of acetylimidazole (1.32 g, 12 m mol) in tetrahydrofuran (15 ml) was added dropwise. After stirring the reaction mixture for 10 minutes, a saturated ammonium chloride solution was added and the resulting mixture was stirred at room temperature. The resultant was diluted with water and extracted with ethyl acetate. The organic layer was washed with a saturated NaCl solution, dried over sodium sulfate and distilled off under reduced pressure to remove the solvent. The residue was subjected to a silica gel column chromatography (2.5×40 cm; ethyl acetate: hexane=1:3) to obtain dimethyl (R)-N-tert-butoxycarbonyl-3-acetylaspartate (1.16 g, 38%) as colorless oil. After stirring for 20 minutes at -40° C. was added dropwise After stirring the reaction mixture for 10 minutes the resulting mixture was stirred at room temperature extracted with ethyl acetate The organic layer was washed with a saturated NaCl solution dried over sodium sulfate distilled off under reduced pressure to remove the solvent