Sulfuric Acid → (-)-methyl(5R)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxylate

Participants

Reaction Steps

A solution of (5R)-(−)-3-[3-fluoro-4-iodophenyl]-5-hydroxymethyl-2-oxazolidinone (Step 1, 7.61 g, 22.58 mmol) in acetone (150 mL) at −10° C. was treated with a mixture of CrO3 (6.21 g, 62.1 mmol) in sulfuric acid (6M, 16.9 mL, 101 mmol) dropwise over 15 minutes. The resulting mixture was allowed to slowly warm to ambient temperature with vigorous stirring (slight exotherm to 35° C.) and was stirred for an additional 16 hours. The mixture was then treated with isopropanol (35 mL), diluted with saline (150 mL) and diethyl ether (150 mL), stirred until all solids are dissolved, and the layers are separated. The aqueous phase was extracted with diethyl ether (100 mL), and the combined organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude carboxylic acid intermediate which was taken up in methanol (225 mL) and treated with concentrated sulfuric acid (8 drops). The resulting homogeneous mixture was stirred at ambient temperature for 20 hours and was then concentrated under reduced pressure to give the crude methyl ester product which was chromatographed on two Flash 40M 90 g silica gel (32-63 μm) cartridges, eluting with a gradient of ethyl acetate/heptane (20/80-40/60). Pooling and concentration of those fractions with an Rf=0.36 by TLC (ethyl acetate/hexane, 50/50) gives the title compound, mp 106-109° C.; MS (ESI+) for C11H9FINO4 m/z 366 (M+H)+; [α]25D=−30 (c 0.93, DMSO).

Provenance & Evidence