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

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

Procedure: To a solution of hexamethyldisilazane (88 mL, 0.421 mol), in THF (500 mL) at −30° C. was added BuLi (2.5M in hexanes, 169 mL, 0.423 mol) and the mixture stirred at this temperature for 15 minutes before cooling to −78° C. A solution of dimethyl N-(tert-butoxycarbonyl)-L-aspartate (Preparation 70, 50 g, 0.19 mol) in THF (200 mL) was added slowly over 15 minutes and the reaction stirred at −78° C. for 2 hours. MeI (14.3 mL, 0.23 mol) was added over 30 minutes and the reaction continued stirring at −78° C. for 18 hours. The reaction was quenched by pouring into an aqueous solution of KHSO4 (80 g in 600 mL, pH=3). THF was then removed in vacuo and the product extracted into EtOAc. The organic layer was collected, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-10% EtOAc in heptane to afford the title compound as a mixture of diastereomers in a ratio 7:3. the reaction stirred at −78° C. for 2 hours the reaction continued stirring at −78° C. for 18 hours The reaction was quenched by pouring into an aqueous solution of KHSO4 (80 g in 600 mL, pH=3) THF was then removed in vacuo the product extracted into EtOAc The organic layer was collected washed with brine dried over Na2SO4 concentrated in vacuo The residue was purified eluting with 0-10% EtOAc in heptane