反应详情

A solution of 4-fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester (intermediate 16) (580 mg, 1.32 mmol), 4-carboxymethylpiperidine-1-car-boxylic acid tert-butyl ester (640 mg, 2.63 mmol), HBTU (1.1 g, 2.9 mmol), and N,N-diisopropylamine (1.2 ml, 6.89 mmol) in 12 ml of dimethylformamide, in a test tube equipped with a magnetic bar, is stirred for 3 days at room temperature. 200 ml of water are added to the reaction medium and the mixture is extracted with ethyl acetate. The organic phase is then washed with water and with saturated sodium chloride solution, and then dried over magnesium sulfate and evaporated. The residue obtained is taken up in ethyl acetate and purified on a Varian flash cartridge containing 50 g of silica of porosity 15-35μ, with a gradient of from 5% to 30% of ethyl acetate in cyclohexane, over 100 minutes. After evaporating off the solvent, 700 mg of 4-{[6-(4-fluorobenzenesulfonyloxy)benzothiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester are obtained (yellow oil) in a yield of 96%.

1. extractionthe mixture is extracted with ethyl acetate
2. washThe organic phase is then washed with water and with saturated sodium chloride solution
3. dry with materialdried over magnesium sulfate
4. customevaporated
5. customThe residue obtained
6. custompurified on a Varian flash cartridge
7. additioncontaining 50 g of silica of porosity 15-35μ
8. waitwith a gradient of from 5% to 30% of ethyl acetate in cyclohexane, over 100 minutes
9. customAfter evaporating off the solvent, 700 mg of 4-{[6-(4-fluorobenzenesulfonyloxy)benzothiazol-2-ylcarbamoyl]methyl}piperidine-1-carboxylic acid tert-butyl ester
10. customare obtained (yellow oil) in a yield of 96%