Sodium Chloride → 4-[(1R,2S)-3-(3,5-Difluorophenyl)-1-hydroxy-2-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Participants

Reaction Steps

Dissolve (R)-tert-butyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate (1.60 g, 6.98 mmol) and 1,3-difluoro-5-(2-nitroethyl)-benzene (1.40 g, 7.48 mmol) in dry tetrahydrofuran (14 mL) and add 1 M tetrabutylammonium fluoride (TBAF) in tetrahydrofuran (7.0 ml, 7.0 mmol) in one portion. Stir the resulting mixture for 30 minutes and then dilute with ethyl acetate. Quickly shake the mixture with water and then add a small amount of saturated aqueous sodium chloride. Discard the aqueous phase and wash the organic phase again with water (twice) followed by saturated aqueous sodium chloride. Dry the organic solution over magnesium sulfate (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 ethyl acetate:hexanes) to give the coupling product as an approximately ˜80:20 mixture of diastereomers (2.45 g, 84%). Isolate the major isomer by recrystallization of the diastereomeric mixture from dichloromethane (dichloromethane)/hexanes or diethyl ether/hexanes) to give 1.26 g of the desired compound as a white crystalline solid.

Provenance & Evidence