Imidazole → 4-[3-[(Tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoronitrobenzene

Participants

Reaction Conditions

Reaction Steps

A solution of 3-fluoro-4-(3-hydroxy-1-azetidinyl)nitrobenzene (5.51 g, 26.0 mmol) in N,N-dimethylformamide (104 mL) under nitrogen was cooled to 0° C. with an ice bath and treated with imidazole (1.86 g, 27.3 mmol) and then tert-butyldimethylsilyl chloride (4.12 g, 27.3 mmol). The reaction mixture was stirred at 0° C. for 30 min and then at room temperature overnight. TLC analysis (5% methanol/chloroform) at this time revealed a small amount of starting material still remained. An additional amount of tert-butyldimethylsilyl chloride (0.392 g) was added. After stirring overnight, TLC analysis indicated the reaction was complete. The reaction mixture was diluted with water (500 mL) and extracted with dichloromethane (4×70 mL). The combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to a yellow solid. Chromatography over silica gel (200 g), eluting with 5% and 10% ethyl acetate/hexane, afforded, after concentration of appropriate fractions, 6.30 g (74%) of the title compound as a yellow solid with mp 98.5°-99.5° C. and MS(EI) 326 (M+).

Provenance & Evidence