Diisopropylethylamine → [4-(1-Hydroxy-3-cyclohexylprop-2-ylaminomethyl)-2-(2-methylphenyl)benzoyl]methionine

Participants

Reaction Steps

A mixture of [4-formyl-2-(2-methylphenyl)benzoyl]methionine ethyl ester (614 mg, 1.54 mmol), prepared according to Example 158F except substituting [4-hydroxmethyl-2-(2-methylphenyl)benzoic acid for 4-hydroxymethyl-2-phenylbenzoic acid in Example 158E, (S)-(+)-2-amino-3-cyclohexyl-1-propanol hydrochloride (357 mg, 1.84 mmol) and diisopropylethylamine (0.135 mL, 0.77 mmol) in toluene was refluxed for 5 hours using a Dean-Stark apparatus. The reaction mixture was cooled to ambient temperature and diluted with ethanol. Sodium cyanoborohydride (145 mg) and o-bromocresol green was added. The reaction mixture was stirred while acidity was maintained using HCl-ethanol. The reaction was quenched with saturated aqueous potassium carbonate and the mixture was extracted with dichloromethane (2×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (5% methanol-chloroform) gave the desired compound (840 mg).

Provenance & Evidence