1-Bromo-3-fluorobenzene → HCID 67028682, compound

Participants

Reaction Conditions

Reaction Steps

In step 3-2, a solution of 3-fluoro-1-bromo benzene (4.0 g, 22.9 mmol) in THF (10 mL) was cooled to −60° C. To this solution n-BuLi in hexanes solution (1.6 M hexanes, 14.3 ml, 22.9 mmol) was added over 12 minutes allowing for a gradual temperature ramp (2° C./minute) until a net internal temperature of −40° C. was obtained and all the n-BuLi was added. The reaction mixture was then allowed to warm over a 30 minute period until an internal temperature of −22° C. was reached, then the resulting solution (dark in color) was cooled to −45° C. and then a solution of (S)-tert-butyl 2-oxo-3-(triisopropylsilyloxy)pyrrolidine-1-carboxylate (2.0 grams, 5.6 mmoles) in THF (10 mL) was added over 6 minutes (do not allow the internal temperature to exceed −40° C. during this addition event). The mixture was then allowed to warm to −20° C. over a 35 minute period and the temperature was then held at −20° C. for 2 hours. The reaction mixture was then quenched with cold saturated ammonium chloride aqueous solution (150 mL), warmed to room temperature and extracted with ethyl acetate (3×150 mL). The organic extracts were combined, concentrated using a rotary evaporator and purified using flash chromatography (5% ethyl acetate in hexanes to 10% ethyl acetate in hexanes over a 30 minute gradient) yielding the racemate of (3S)-tert-butyl 2-(3-fluorophenyl)-2-hydroxy-3-(triisopropylsilyloxy)pyrrolidine-1-carboxylate (3-2) as an oil. 1H NMR (400 MHz, D6 acetone) δ ppm 7.92-7.23 (m, 4H), 5.80 (br s, 1H), 5.10 (app t, J=8.2, 1H), 3.20-2.95 (m, 2H), 2.05-1.95 (m, 2H), 1.35 (s, 9H), 1.21-0.99 (m, 21H). LCMS observed m/z 737.5 major ion.

Provenance & Evidence