Methanol → 2-[N-{(2S,3R)-4-(4-Chlorophenyl)-3-(4-biphenylyl)-2-butyl}aminocarbonyl]cyclobutane-1-carboxylic acid methyl ester

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Reaction Steps

To a solution of 56 mg (0.31 mmol) trans-1,2-cyclobutanedicarbonylchloride in 3 mL of ethyl ether at -10° C. was added a solution of 106 mg (0.31 mmol) of (1RS,2SR)-2-(4-biphenylyl)-3-(4-chlorophenyl)-1-methylpropylamine hydrochloride, prepared by the procedures described in Example 114 of European Patent Application EP 611749, published Aug. 24, 1994, 0.25 mL (6.2 mmol) of methanol and 65 μL (0.46 mmol) of triethylamine in 3 mL of CH2Cl2 dropwise. The mixture was stirred overnight during which time the cold bath melted. The mixture was poured into a separatory funnel containg 50 mL of ethyl ether and 20 mL of H2O and the phases were separated. The organic phase was extracted with 1N aqueous HCl and then dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on SiO2 eluting with 40% ethyl acetate in hexanes to give 52 mg (35%) of the title compound as a 1:1 mixture of diastereomers. 1H NMR (CDCl3) δ 7.57 (m, 2H), 7.49 (m, 2H), 7.43 (m, 2H), 7.32 (m, 1H), 7.13 (m, 4H), 6.92 (m, 2H), 5.74 (bd, 1H), 4.33 (m, 1H), 3.64, 3.67, (2s, total 3H), 2.87-3.35 (m, 5H), 1.91-2.38 (m, 4H), 1.02 (2d, total 3H). MS (DCl NH3) m/e (M+H)+.

Provenance & Evidence