Sodium Bicarbonate → 2-Fluoro-6,n,n-trimethyl-3-morpholin-4-ylbenzamide

Temperatur

0 °C

393 mg (1.10 mmol) of N,N′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate) was added to 7 ml of an acetonitrile solution containing 458 mg (1.84 mmol) of the 2, N,N-trimethyl-5-morpholin-4-ylbenzamide obtained in Step B of Example 80 under cooling on ice. The obtained mixture was stirred at 0° C. for 1 hour, then at a room temperature for 1 hour, then at 50° C. for 1 hour, then at 80° C. for 2.5 days, and then under heating to reflux for 2 hours. Thereafter, 357 mg (1.0 mmol) of N,N′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate) was further added to the reaction solution, and the obtained mixture was further stirred for 20 minutes. Thereafter, a saturated sodium bicarbonate aqueous solution was added to the reaction solution, and the mixture was then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and was then concentrated. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:3 to 1:1), so as to obtain 25.8 mg (5.3%) of 4-fluoro-2,N,N-trimethyl-5-morpholin-4-ylbenzamide in the form of an oily substance, and also obtain 35.1 mg (7.2%) of 2-fluoro-6,N,N-trimethyl-3-morpholin-4-ylbenzamide in the form of an oily substance.

1. temperatureunder cooling on ice
2. waitat a room temperature for 1 hour
3. waitat 50° C. for 1 hour
4. waitat 80° C. for 2.5 days
5. temperatureunder heating
6. temperatureto reflux for 2 hours
7. stirringthe obtained mixture was further stirred for 20 minutes
8. extractionthe mixture was then extracted with ethyl acetate
9. dry with materialThe extract was dried over anhydrous sodium sulfate
10. concentrationwas then concentrated
11. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:3 to 1:1)

ORD-Eintrag

ord-fe6ed1284d814452a0c7f1e5510c64a0

Quelldatensatz

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08143274B2