Trifluoroacetic acid → 4-Bromo-3-hydroxypyridine

Participants

Reaction Steps

(S)-1-t-Butoxycarbonyl-2-pyrrolidinemethanol (792 mg, 3.94 mmol), 4-bromo-3-pyridinol (685 mg, 3.94 mmol), DEAD (485 uL, 4.33 mmol) and PPh3 (1.14 g, 4.33 mmol) were allowed to react as described in Example 2a. The crude product was directly treated with trifluoroacetic acid (5 mL) at room temperature for 3 hours. The trifluoroacetic acid was removed under reduced pressure, and water (8 mL) was added. The mixture was extracted with EtOAc (2×20 mL), and the resultant aqueous layer was basified with excess solid sodium bicarbonate. The resultant slurry was washed extensively with EtOAc (4×10 mL). The combined organic layers were dried (Na2SO4) and evaporated. The crude product was purified by flash chromatography on silica gel eluting with CHCl3 /MeOH/NH4OH (10:1.5:0.02 and 10:1.5:0.1) to provide 371 mg (37% yield from 4-bromo-3-pyridinol) of the title compound. TLC Rf 0.16 (10:1:0.02 CHCl3 /MeOH/NH4OH). MS (DCI/NH3) m/e 257 with 79Br and 259 (M+H)+ with 81Br. 1H NMR (CDCl3, 300 MHz) δ: 8.25 (s, 1H, ArH), 8.08 (d, J=6.6 Hz, 1H, ArH), 7.48 (d, J=6.6 Hz, 1H, ArH), 4.28 (dd, J=4.8, 10.2 Hz, 1H, OCHH), 4.17 (dd, J=6.3, 10.2 Hz, 1H, OCHH), 3.90-3.80 (m, 1H, NCH), 3.30-3.14 (m, 2H, NCH2), 2.18-1.80 (m, 4H, 2CH2).

Provenance & Evidence