反应详情

Methanesulfonic acid 5-bromo-2-propionyl-phenyl ester, prepared as described in U.S. Ser. No. 09/308,954, filed May 8, 1997 as Attorney Docket No. PC9798, 30 grams (97.66 mmol) was combined with 4-fluorophenyl hydrazine hydrochloride (31.76 g, 175.33 mmol) and sodium acetate (30 g, 364 mmol) in mesitylene (400 mL). The reaction mixture was heated to reflux in a Dean-Stark apparatus for 96 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The crude product was diluted with 500 mL of diethyl ether and 600 mL of water. Organic layer was separated and aqueous layer extracted with 500 mL of ethyl acetate. Combined organic extracts were washed with water (2×600 mL), brine (1×200 mL), dried over MgSO4 and concentrated which gave a brown-red oil. Hexane (600 mL) was added to crude reaction product and the mixture boiled in a steam bath for a few minutes. This was followed by cooling still the heterogeneous mixture to room temperature and allowing to stand at room temperature for 12-14 hours. The reaction mixture was filtered, undissolved solid washed with additional hexane and filtrate which contained approximately 80% pure desired product concentrated in vacuo to give brown-yellow solid. Purification of this product on silica gel column and eluting with 15% ethyl acetate/85% hexane gave 14.1 grams of light brown-tan solid. Recrystallization from hexane gave light tan needles. mp=72-73° C.; MS (APCI) m/z 319 (base).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux in a Dean-Stark apparatus for 96 hours
3. concentrationconcentrated under reduced pressure
4. additionThe crude product was diluted with 500 mL of diethyl ether and 600 mL of water
5. customOrganic layer was separated
6. extractionaqueous layer extracted with 500 mL of ethyl acetate
7. washCombined organic extracts were washed with water (2×600 mL), brine (1×200 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated which
10. customgave a brown-red oil
11. customreaction product
12. waitthe mixture boiled in a steam bath for a few minutes
13. temperatureby cooling still the heterogeneous mixture to room temperature
14. filtrationThe reaction mixture was filtered
15. washundissolved solid washed with additional hexane and filtrate which
16. concentrationconcentrated in vacuo
17. customto give brown-yellow solid
18. customPurification of this product on silica gel column
19. washeluting with 15% ethyl acetate/85% hexane