Dimethyl Sulfate → (3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

10 g of (S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)pyrrolidin-2-one (1-a, R1=pivaloyl) were dissolved in 150 ml toluene. The mixture was cooled to about 0° C. and 71.5 ml potassium bis(trimethylsilyl)amide solution (0.5 M in toluene) were added. After 15 min, 11 ml dimethyl sulphate were added and the mixture was stirred for a further hour. The reaction was quenched with ammonium chloride solution and extracted with ethyl acetate. The combined organic phases were concentrated to dryness to obtain 15.3 g of crude (3R,5S)-5-biphenyl-4-ylmethyl-1-(2,2-dimethylpropionyl)-3-methylpyrrolidin-2-one. According to HNMR analysis, on the crude, the ratio of diastereoisomers is 83:17 [(3R,5S):(3S,5S)]. Spectroscopic data for (2-a, R1=Pivaloyl) is reported in Example 5-1, Method 1. Spectroscopic data for (2-b, R1=Pivaloyl) is reported in Example 5-2.

Provenance & Evidence