Sodium hydride → 3,5-Bis(trifluoromethyl)benzyl 4-({[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}methyl)piperidine-1-carboxylate

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Reaction Steps

To a solution of [3,5-bis(trifluoromethyl)phenyl]methanol (17 mg) in tetrahydrofuran (5 ml) was added sodium hydride (5 mg, 60% dispersion in mineral oil). The mixture was allowed to stir for 5 min, and then 4-nitrobenzyl 4-({[4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoyl]amino}methyl)piperidine-1-carboxylate (20 mg) was added. The reaction mixture was stirred overnight at room temperature, and then was concentrated. The residue was purified by reverse-phase HPLC on a Biotage Parallex Flex, Kromasil C18 21×100 mm column, eluting at 15 mL/min with 90% water (0.1% TFA) to 95% acetonitrile (0.1% TFA) over 10 min, hold for 2 min, then back to 90% water over 0.5 min, hold for 0.5 min, to provide the title compound (5 mg, 21%). Mass spectrum (ESI) 673.1 (M+1). NMR signals are doubled and broadened because of restricted rotation about the amide C—N bond. 1H NMR (500 MHz, CDCl3): δ 8.34 (d, J=8 Hz, 2H), 7.95 (m, 2H), 7.93 (s, 1H), 7.83 (s, 1H), 7.80 (s, 2H), 7.52 (s, 1H), 6.316 (app t, 1H), 5.23 (s, 2H), 4.23 (m, 2H), 2.82-2.90 (m, 2H), 1.89-1.93 (m, 1H), 1.83 (m, 3H), 1.73 (m, 3H), 1.46 (d, J=7 Hz, 6H), 1.21-1.31 (m, 4H).

Provenance & Evidence