Pyridine → Rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea

Temperatur

25 °C

A cooled (0° C) solution of rac-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetic acid (Example 6; 100 mg, 0.30 mmol) in fluorobenzene (2.5 mL) and N ,N-dimethylfor m namide (1.8 μL). was treated with a 2.0 M solution of oxalyl chloride in dichloromethane (0.18 mL, 0.36 mmol). Immediately a vigorous gas evolution was observed, and the mixture was stirred at 25° C. for 1 h and became light yellow in color. Methyl urea (97 mg, 0.90 mmol) was then added and after the reaction was heated at 70° C. for 10 min, pyridine (0.048 mL, 0.60 mmol) was added and the reaction was maintained at 70° C. for 1 h. The cooled mixture was diluted with ethyl acetate (5 mL) then was filtered through Celite to remove insoluble materials and the filtrate concentrated in vacuo. The concentrate was washed with 3N hydrochloric acid (1×20 mL), saturated sodium bicarbonate (1×15 mL) and brine (1×15 mL), then was dried over sodium sulfate, filtered and evaporated under reduced pressure. The product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate) to provide rac-1-[(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxy-acetyl]-3-methyl-urea (78 mg, 67% yield) as a white foam: FAB-HRMS m/e calculated for C16H21N2O5SCl (M+H)+389.0938, found 389.0943.

1. temperatureafter the reaction was heated at 70° C. for 10 min
2. temperaturethe reaction was maintained at 70° C. for 1 h
3. filtrationthen was filtered through Celite
4. customto remove insoluble materials
5. concentrationthe filtrate concentrated in vacuo
6. washThe concentrate was washed with 3N hydrochloric acid (1×20 mL), saturated sodium bicarbonate (1×15 mL) and brine (1×15 mL)
7. dry with materialwas dried over sodium sulfate
8. filtrationfiltered
9. customevaporated under reduced pressure
10. customThe product was purified by chromatography (Biotage Flash 40S column, 50/50 hexanes/ethyl acetate)

ORD-Eintrag

ord-ece7149cbe3240b9a436fd8f07c48bb3

Quelldatensatz

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06486184B2