Methanol → HCID 131725240, compound

Participants

Reaction Steps

A solution of (±)-trans-3-[4-(4-chlorobenzyl)piperidin-1-yl]-4-[3-(3,4,5-trimethoxyphenyl)-ureido]-pyrrolidine-1-carboxylic acid tert-butyl ester (410 mg, 0.68 mmol) in 2% HCl/MeOH (70 mL) was stirred at room temperature overnight. The MeOH 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 on alumina with CH2Cl2 followed by 50:0.95:0.05-5:0.95:0.05 CH2Cl2:MeOH:NH4OH gave the free base (±)-trans-1-{4-[4-(4-chlorobenzyl)piperidin-1-yl]-pyrrolidin-3-yl}-3-(3,4,5-trimethoxyphenyl)urea (225 mg, 0.45 mmol) as a white solid. A solution of the free base (25 mg, 0.05 mmol) in CH2Cl2 was treated with 1 N HCl in Et2O (0.15 mL, 0.15 mmol) and concentrated to give the product (27 mg, 68%) as a yellow solid: mp 157.0-170.0° C.; IR 3416 (br), 2935, 1686, 1606, 1554, 1507 cm−1; 1H NMR [(CD3)2SO] δ 1.50-1.81 (m, 5H), 2.60 (d, J=6.6 Hz, 2H), 3.00-3.99 (m, 20H), 4.68 (m, 1H), 6.76 (s, 2H), 7.21 (m, 2H), 7.32 (m, 2H); MS m/z 504 (M+H)+. Step A: Preparation of (±)-trans-3-[4-(4-chlorobenzyl)piperidin-1-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Provenance & Evidence