Formaldehyde → tert-Butyl alpha-(1-Hydroxymethyl)-3-(2-methylpropyl)-2-oxo-1-(2-phenylethyl)-3-pyrrolidineacetate

Participants

Reaction Conditions

Reaction Steps

A cold (-78° C.) solution of tert-butyl 3-(2-methylpropyl)-2-oxo-1-(2-phenylethyl)-3-pyrrolidineacetate (EXAMPLE 1, step 3; 2.00 g, 5.56 mmol) in dry THF (20 mL) is treated with the dropwise addition of LDA (3.20 mL, 6.40 mmol, 2.0N). The solution is maintained at -78° C. for 30 min and then warmed to -30° C. Gaseous formaldehyde (generated by heating 834 mg of paraformaldehyde at 160° C. to provide approximately 28 mmol) is bubbled through the enolate solution. The solution is maintained at -30° C. for 1 hour and then quenched with saturated aqueous NH4Cl (5 mL) and diluted with H2O (20 mL). The product is extracted into EtOAc (3×50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to provide 2.52 g of a yellow solid which is purified by silica gel chromatography (100 g SG; 25% EtOAc/hexane) to give 1.43 g (83%) of the title compound as a golden oil. Another fraction containing 375 mg of a mix of both diastereomers is also recovered. Spectral data for the title compound:

Provenance & Evidence