反应详情

1-(2-Chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid (2.82 g) were dissolved in THF (30 ml) under an argon atmosphere at RT and then sequentially treated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (3.26 g), (4-amino-phenyl)-acetic acid ethyl ester (1.536 g) and N-methyl morpholine (1.04 ml). The reaction mixture was stirred 12 h at RT, and 1 h at reflux to complete the reaction. The mixture was partitioned between AcOEt and 1N HCl/water, the layers were separated; the organic layer was dried over sodium sulphate and then removed in vacuo. The residue was purified by chromatography on silica gel (CH2Cl2/AcOEt, 19/1 to 9/1) to give the desired (4-{[1-(2-chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carbonyl]-amino}-phenyl)-acetic acid ethyl ester (2.47 g) which was directly used in the next step.

1. temperature1 h at reflux
2. customthe reaction
3. customThe mixture was partitioned between AcOEt and 1N HCl/water
4. customthe layers were separated
5. dry with materialthe organic layer was dried over sodium sulphate
6. customremoved in vacuo
7. customThe residue was purified by chromatography on silica gel (CH2Cl2/AcOEt, 19/1 to 9/1)