Formaldehyde → (R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylester

Participants

Reaction Conditions

Reaction Steps

The mixture of (R/S)-3-Benzoyl-(S)-5-biphenyl-4-ylmethyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (4a, R1=t-butoxycarbonyl, R4=phenyl) (0.455 g, 1 mmol), paraformaldehyde (60 mg, 2 mmol) and potassium-tert-butoxide (0.148 g, 1.3 mmol) in 5 mL dry DME is stirred for 2 hours at 20° C. Then the reaction mixture is diluted with 5 mL saturated aqueous ammonium chloride solution and stirred for 15 min, stop stirring, and remove the lower aqueous layer. the organic phase is then concentrated in vacuo. ethyl acetate 10 mL is added, filtered and the filtrate concentrated and purified by column chromatography eluting with 5:1 heptane/ethyl acetate to afford (R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylester (1a, R1=t-butoxycarbonyl). Spectroscopic data as reported in WO2009/090251 (Example 23, Method 1).

Provenance & Evidence