Water → (2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of (2S,3R)-3-(tert-Butyldimethylsilanyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (51A) (195 mg, 0.54 mmol) in THF (6 mL) at −78° C. was added a 1.8 M solution of LDA (0.66 mL, 1.19 mmol). After stirring for 1.5 h at −78° C. and 0.5 h at −30° C., the reaction was cooled again to −78° C. and iodomethane (0.2 mL, 3.21 mmol) was added. The mixture was stirred at −78° C. for 1 h and at −20° C. for 4 h. After warming to rt, water and EtOAc were added and the layers were separated. The organic layer was washed with brine, dried (Na2SO4), filtered then concentrated under reduced pressure. The resulting residue was purified via preparative HPLC (Luna C-18, 21.1×100 mm, eluting with 75-100% solvent B (A=90% H2O-10% MeOH-0.1% TFA and B=10% H2O-90% MeOH-0.1% TFA) over 12 min; Flow rate at 20 mL/min. UV detection at 220 nm) to provide the title compound (36 mg). LC/MS m/z 374 [M+H]+.

Provenance & Evidence