Hydrochloric Acid → 2-{[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-methyl}-4-trifluoromethyl-phenyl-cyclobutyl-methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{[(3,5-bis-trifluoromethyl-benzyl)(2-methyl-2H-tetrazol-5-yl)amino]-methyl}-4-trifluoromethyl-benzaldehyde (1.5 g; 2.9 mmol) in tetrahydrofuran (14 mL) at −10° C. was added dropwise cyclobutylmagnesium bromide (9 mL; 5.4 mmol; 0.6M solution in tetrahydrofuran). The reaction was stirred at −10° C. for 1.5 hours. To quench the reaction, at 0° C. was added aqueous 2N hydrochloric acid. Reaction extracted with ethyl acetate. The organic was washed with aqueous 2N hydrochloric acid, water and brine. It was dried sodium sulfate and concentrated under reduced pressure. The residue was purified by 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 15-70% ethyl acetate in heptane) to give 420 mg (25% yield) as a gum. MS (ES−): Calc; 567.4, Found: 612.6 (M+HCO2). 1H NMR (400 MHz, CDCl3) δ ppm 7.78 (s, 1H), 7.66 (s, 2H), 7.52 (d, J=8.30 Hz, 1H), 7.49 (d, J=8.30 Hz, 1H), 7.35 (s, 1H), 4.86 (q, J=15.77 Hz, 2H), 4.86 (s, 1H), 4.77 (q, J=15.77, 16.18 Hz, 2H), 4.20 (s, 3H), 2.68 (m, 1H), 2.05-1.96 (m, 2H), 1.93-1.76 (m, 3H), 1.70 (m, 1H).

Provenance & Evidence