反应详情

2-Chlorosulfonylmethyl-3-methylbutyric acid tert-butyl ester (0.072 g) [preparation described in WO-A-98/05635] was added as a solution in dichloromethane (2 ml) to a stirred mixture of 1-(4-pyridin-3-yl-phenyl)piperazine (0.053 g) and triethylamine (40 μl) and the resultant solution stirred at room temperature for 2 h. Trifluoroacetic acid (4 ml) was then added dropwise, and the mixture stirred for a further 2 h. The solvent were removed under reduced pressure and the residue azeotroped with 1:1 dichloromethane/hexane (2×10 ml). The residue was then diluted with diethyl ether (20 ml) and extracted with 1 M sodium hydroxide (10 ml) followed by 0.5 M sodium hydroxide (10 ml). The combined aqueous extracts were then washed with diethyl ether (20 ml), then cautiously acidified to pH 5 with acetic acid, forming a precipitate. The mixture was then extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with water (2×10 ml), saturated brine (10 ml), dried (Na2SO4) and reduced in vacuo to give the title compound as a pale green solid (0.085 g, 93%).

1. customThe solvent were removed under reduced pressure
2. customthe residue azeotroped with 1:1 dichloromethane/hexane (2×10 ml)
3. additionThe residue was then diluted with diethyl ether (20 ml)
4. extractionextracted with 1 M sodium hydroxide (10 ml)
5. washThe combined aqueous extracts were then washed with diethyl ether (20 ml)
6. customforming a precipitate
7. extractionThe mixture was then extracted with ethyl acetate (3×20 ml)
8. washThe combined organic extracts were washed with water (2×10 ml), saturated brine (10 ml)
9. dry with materialdried (Na2SO4)