Methyl Acetate → HCID 86705559, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (16.70 mL, 119.1 mmol) in THF (80 mL) at 0° C. was added dropwise 2.5M n-butyllithium (48.82 mL, 122.0 mmol) and stirring was continued for 15 min. The solution was cooled to −78° C. and methyl acetate (9.219 mL, 116.2 mmol) was added dropwise and stirring continued for 30 min. A solution of Ti(O-iPr)3Cl (58.30 mL, 244.1 mmol) in THF (20 mL) was introduced dropwise at −78° C. and stirring was continued for 45 min. A solution of 378 (16 g, 58.12 mmol) in THF (20 mL) was then added dropwise and stirring was continued for 3 h. The reaction was quenched at −78° C. by dropwise addition of satd. aq. NH4Cl and warmed to RT. The mixture was thrice extracted with EtOAc, washed with brine, dried (MgSO4), and concentrated. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (20 to 60% EtOAc) to afford 8.67 g (43%) of (R)-methyl 3-(4-(difluoromethoxy)phenyl)-3-((S)-1,1-dimethylethylsulfinamido)propanoate (380) as a low melting white solid along with 9.67 g impure material.

Provenance & Evidence