Dimethyl Sulfoxide → 6-Fluoro-5-Hydroxy-4-Nitro-Hexanoic Acid Methylamide

Participants

Reaction Conditions

Reaction Steps

To a clear solution of oxalyl chloride (2.0 M oxalyl chloride in dichloromethane, 0.868 g, 6.84 mmol) at −74° C. was added anhydrous DMSO (1.06 mL, 14.9 mmol) dropwise over 10 minutes while maintaining the internal temperature <−60° C. The white suspension was stirred for 15 min, then 2-fluoroethanol (0.273 mL, 4.65 mmol) was added dropwise while maintaining the internal temperature <−65° C. The yellow suspension was stirred for 20 minutes and then diluted with dichloromethane (19.5 mL), followed by the addition of anhydrous Et3N (3.90 mL, 28.0 mmol). The reaction mixture was stirred for 15 min at −71° C. and then allowed to warm to 0° C. and stirred at 0° C. for 2 h. To the reaction mixture was added a solution of N-methyl-4-nitro-butyramide (0.570 g, 3.90 mmol) in dichloromethane (2.3 mL). The reaction mixture was stirred at 0° C. for 1 h and then stirred at room temperature overnight. The mixture was concentrated to a white residue, diluted with ethyl acetate (50 mL), and the organic layer was washed with water (25 mL). The aqueous layer was then extracted with ethyl acetate (2×40 mL) and the combined organic layers were dried over MgSO4, concentrated and the residue was purified by flash chromatography (silica gel, gradient elution with EtOAc:Hexanes, 1:1 to 4:1) to give 0.325 g (40%) of the titled product as a colorless viscous oil. 1H NMR (CDCl3): 6.88 (br s, NH, 1H), 6.31 (br s, NH, 1H), 5.20-4.20 (m, 5H), 2.40-2.15 (m, 4H).

Provenance & Evidence