反应详情

温度

0 °C

To a solution of 5-(benzyloxy)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxypyrimidine-4-carboxylic acid (28-02) (150 mg, 342 μmol, Eq: 1.00) and N-(2-(tert-butyldimethylsilyloxy)ethyl)-1,1,1-trifluoropropan-2-amine (41) (102 mg, 376 μmol, Eq: 1.1) in pyridine (1.5 ml) was added POCl3 (157 mg, 95.6 μl, 1.03 mmol, Eq: 3.00) at −10° C. (ethylene glycol-dry-ice bath), then the reaction mixture was stirred at 0° C. for 2 hr. Ice cooled-water was slowly added to the reaction mixture at 0° C., which was extracted with ethyl acetate. The organic layer was washed with aqueous saturated NaHCO3 solution, dried (MgSO4), concentrated, and chromatographed (silica gel, gradient 5 to 50% ethyl acetate-hexane) to obtain 5-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-2-((1-(4-chlorophenyl)cyclopentyl)methyl)-6-hydroxy-N-(1,1,1-trifluoropropan-2-yl)pyrimidine-4-carboxamide (42) (oil, 138 mg, 199 μmol, 58.3% yield).

1. additionwas slowly added to the reaction mixture at 0° C.
2. extractionwhich was extracted with ethyl acetate
3. washThe organic layer was washed with aqueous saturated NaHCO3 solution
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. customchromatographed (silica gel, gradient 5 to 50% ethyl acetate-hexane)