(3S)-3-ethoxypyrrolidine → (S)-7-benzyloxy-4-(3-ethoxy-pyrrolidin-1-yl)-2-methyl-quinoline hydrochloride

Participants

Reaction Conditions

Reaction Steps

A mixture of 436 mg (1.5 mmol) of 7-Benzyloxy-4-chloro-2-methyl-quinoline, product of example 1d), and 1.75 g (15 mmol) of (S)-3-ethoxypyrrolidine, prepared according to Tetrahedron Lett., 1995, 2745, was heated at 80° C. (oil bath temperature) under an argon atmosphere for 18 h after which time the reaction was completed according to HPLC analysis. The excess (S)-3-ethoxy-pyrrolidine was distilled off, and the residue was partitioned between EtOAc and water. The layers were separated, the organic layer was washed with water then saturated NaCl solution, dried over magnesium sulphate and concentrated in vacuo. The residue was taken-up in MeOH (1 ml) diluted with diethyl ether (30 ml) and then treated dropwise at RT under stirring with 0.7 ml of 3N HCL in MeOH. The solvent was removed and the remaining salt triturated with diethyl ether, then filtered off by suction and dried in a high vacuum to give 425 mg (69.7%) of the (S)-7-benzyloxy-4-(3-ethoxy-pyrrolidin-1-yl)-2-methyl-quinoline hydrochloride as a light yellow solid. ISP mass spectrum, m/e: 363.2 (M+1 calculated for C23H26N2O2: 363).

Provenance & Evidence