(S)-tert-butyl 3-formylpyrrolidine-1-carboxylate → (35)-Tert-butyl 3-((3-chloro-4-fluorophenyl)(hydroxy)methyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-tert-butyl 3-formylpyrrolidine-1-carboxylate (67)(367.3 mg, 1.843 mmol) in THF (9.2 mL, 0.2 M) under nitrogen atmosphere cooled to 0° C. and degassed with N2 was added dropwise a THF solution of (3-chloro-4-fluorophenyl)magnesium bromide (4056 μL, 2.028 mmol) and the solution stirred at 0° C. for 3 h. The reaction was then quenched by addition of water (3 mL) THF was removed by rotovap, and the mixture was extracted with EtOAc (2×30 mL). The combined organics were washed with water (2×30 mL) and brine (1×30 mL). The organic extracts were dried (Na2SO4), filtered and concentrated. The crude product was loaded onto an SP1 samplet and purified by chromatography eluting a DCM/acetone gradient (2 to 45% acetone) to afford 364 mg (60%) of 69a/69b as an approximate 1:1 mixture of diastereomers as a clear oil which was used without additional purification.

Provenance & Evidence