反应详情

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)

1. additionadded as a catalyst
2. concentrationThe reaction is concentrated in vacuo
3. dissolutionThe resulting residue is dissolved in dichloromethane
4. stirringThe reaction is stirred at room temperature for 18 h
5. washThe reaction is washed with saturated aqueous sodium bicarbonate
6. extractionthe aqueous portion extracted with 10% isopropanol/dichloromethane
7. concentrationThe combined organic portions are concentrated in vacuo
8. custompurified via radial chromatography
9. washeluting with 2 M ammonia in methanol and dichloromethane
10. dissolutionThe purified free base is dissolved in a minimal amount of dichloromethane
11. additiona slight excess of 1 M HCl in ether is added
12. concentrationThe mixture is then concentrated in vacuo