Toluene → [3-(3,5-Dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanol

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Reaction Steps

A solution of 3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolecarboxylic acid (0.54 g, 1.8 mmol) in THF (9 mL), was stirred as triethylamine (0.25 mL, 1.8 mmol) was added. The solution was cooled in ice bath before the addition of a 1 N solution of isopropylchloroformate in toluene (1.8 mL, 1.8 mmol). The solution was allowed to stir for 30 minutes before being filtered into a solution of sodium borohydride (91 mg, 2.4 mmol) in water (0.62 mL). The mixture was allowed to warm to room temperature and stir for 3 days. The mixture was filtered and the filtrate was partitioned between brine and ethyl acetate. The organic layer was dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (silica gel, hexane to 2:3 ethyl acetate:hexanes) to provide [3-(3,5-dichloro-4-pyridinyl)-5-(1-methylethyl)-4-isoxazolyl]methanol (0.32 g, 57% as 0.3 ethyl acetate). 1H NMR (400 MHz, DMSO-d6): δ 8.79 (s, 2H), 4.96 (t, J=5 Hz, 1H), 4.20 (d, J=5 Hz, 2H), 3.35 (septet, J=7 Hz, 1H), 1.29 (d, J=7 Hz, 6H).

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