反应详情

温度

-10 °C

To a stirred white suspension of 5-benzyloxy-2-[1-(2,5-dichlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid (205) (500 mg, 1.05 mmol) in pyridine (5.5 mL) was added [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropyl-amine (8b) (344 mg, 1.58 mmol), cooled to −10° C., POCl3 (0.3 mL, 3.17 mmol) was added at the same temperature. The mixture was stirred at 0° C. for 2 h. Silica thin layer chromatography was performed (50% ethyl acetate in hexane, Rf=0.8). After completion of the reaction, ice cooled-water (30 mL) was added to the reaction mixture at 0° C., a saturated solution of NaHCO3 (pH˜8) was added, the mixture was extracted with ethyl acetate (4×50 mL), the organic part was dried and concentrated, the crude product was purified by a CombiFlash column (eluted at 30%-50% ethyl acetate in hexane) to get 5-benzyloxy-2-[1-(2,5-dichlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-isopropylamide (206) (250 mg, 35.18%) as a yellow sticky mass.

1. customAfter completion of the reaction, ice
2. additionwas added to the reaction mixture at 0° C.
3. extractionthe mixture was extracted with ethyl acetate (4×50 mL)
4. customthe organic part was dried
5. concentrationconcentrated
6. customthe crude product was purified by a CombiFlash column (eluted at 30%-50% ethyl acetate in hexane)