4-Methylmorpholine → [4-(3-Methanesulfonyl-phenoxy)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone hydrochloride

関与物質

反応手順

4-(3-Methanesulfonyl-phenoxy)-benzoic acid (1.0 mmol) (see Intermediate 13) and oxalyl chloride (2.0 mmol) are combined in dichloromethane (0.10 M), add 1 drop of dimethylformamide added as a catalyst. The solution is stirred at room temperature for 2 h. The reaction is concentrated in vacuo. The resulting residue is dissolved in dichloromethane and added to a stirring solution of (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (1.0 mmol) and N-methylmorpholine (1.0 mmol) in dichloromethane (0.10 M). The reaction is stirred at room temperature for 18 h. The reaction is washed with saturated aqueous sodium bicarbonate and the aqueous portion extracted with 10% isopropanol/dichloromethane. The combined organic portions are concentrated in vacuo and purified via radial chromatography eluting with 2 M ammonia in methanol and dichloromethane. The purified free base is dissolved in a minimal amount of dichloromethane and a slight excess of 1 M HCl in ether is added, followed by hexane. The mixture is then concentrated in vacuo to give the titled compound. MS (m/e): 429.2 (M+1)

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