Tetrahydrofuran → HCID 21193257, compound

Participants

Reaction Steps

A mixture of 4-(3-trifluoromethoxybenzyl)-4-hydroxy-methylpiperidine hydrochloride salt (0.62 g, 2.0 mmol), 1-(4-cyano-benzyl)imidazole-5-carboxyaldehyde (0.45 g, 2.0 mmol; Example 1, Step E), diisopropylethylamine (0.53 mL, 3.04 mmol), anhydrous magnesium sulfate (650 mg), activated molecular sieves 3 A powder (750 mg), and anhydrous methanol (6 mL) was stirred at room temp. overnight. The pH of the mixture was adjusted to ˜5 with addition of glacial acetic acid. To the mixture, a solution of sodium cyanoborohydride in THF (2.2 mL, 1 M, 2.2 mmol) was added slowly over a period of 8 h with a syringe pump, and stirred at room temp. overnight. The product mixture was diluted with chloroform, filtered through Celite. The filtrate was washed with aqueous sodium bicarbonate, brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 5-10% methanol in chloroform gradient. Collection and concentration of appropriate fractions provided the title compound as white solid.

Provenance & Evidence