Methanol → HCID 23587466, compound

Participants

Reaction Steps

A solution of (±)-1-{(1R,2R,4S)-4-(tert-butyl-dimethylsilanyloxymethyl)-2-[4-(4-chlorobenzyl)-piperidin-1-yl]-cyclopentyl}-3-(3,4,5-trimethoxyphenyl)urea (1.13 g, 1.75 mmol) in 1% HCl/EtOH (120 mL) was stirred at room temperature for 1 h. The EtOH was evaporated and the residue was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 and the extracts were washed with brine, dried (MgSO4) and concentrated. Chromatography of the residue with 95:4.75:0.25-90:9.5:0.5 CH2Cl2:MeOH:NH4OH gave the free base (±)-1-{(1R,2R,4S)-2-[4-(4-chlorobenzyl)piperidin-1-yl]-4-hydroxymethyl-cyclopentyl}-3-(3,4,5-trimethoxyphenyl)urea (690 mg, 1.30 mmol) as a yellow solid. A solution of the free base (105 mg, 0.20 mmol) in CH2Cl2 was treated with 1 N HCl in Et2O (0.5 mL, 0.5 mmol) and concentrated to give the product (112 mg, 74%) as a yellow solid: mp 138.0-143.0° C.; IR 3417 (br), 2936, 1687, 1606, 1554, 1507 cm−1; 1H NMR [(CD3)2SO] δ 1.28-2.12 (m, 10H), 2.54 (m, 2H), 2.91 (m, 2H), 3.26-3.59 (m, 8H), 3.71 (s, 6H), 4.34 (m, 1H), 4.70 (br s, 1H), 6.66 (d, J=8.3 Hz, 1H), 6.73 (s, 2H), 7.21 (m, 2H), 7.32 (m, 2H), 8.78 (s, 1H), 10.13 (br s, 1H); MS m/z 532 (M+H)+. Step A: Preparation of (±)-(1R,2R,4R)-4-(tert-butyl-dimethylsilanyloxymethyl)-2-[4-(4-chlorobenzyl)piperidin-1-yl]-cyclopentol

Provenance & Evidence