Hydrochloric Acid → 2-(2,6-Difluoro-phenyl)-8-hydroxy-benzo[d][1,3]oxazin-4-one

3-Triisopropylsilyloxyanthranilic acid (0.8 g), 2,6-difluorobenzoyl chloride (0.71 mL) and triethyl amine/toluene (1/1) (25 mL) were reacted as described under (10). Reaction time 2 days. Extraction between ethyl acetate (100 mL) and HCl (1N,100 mL), followed by separation of the organic layer, drylng over MgSO4, filtering and evaporation gave a crude product which was dissolved in warm THF (20 mL) and precipitated with hexane. The resulting mixture was further purified on a silicagel column using dichloromethane as eluent. The isolated fraction (80 mg) was hydrolysed with 1% HCl in ethanol by stirring for 2 days at RT, and further hydrolysis after addition of HCl (4N, 5 mL) and ethyl acetate (10 mL). The organic layer was separated, evaporated and dried resulting in 2-(2,6-difluoro-phenyl)-8-hydroxy-benzo[d][1,3]oxazin-4-one (32 mg), mp.190-198. LC-MS showed the purity 86% with the corresponding O-triisopropylsilylated product as the impurity.

1. customReaction time 2 days
2. extractionExtraction between ethyl acetate (100 mL) and HCl (1N,100 mL)
3. customfollowed by separation of the organic layer
4. filtrationfiltering
5. customevaporation
6. customgave a crude product which
7. customprecipitated with hexane
8. customThe resulting mixture was further purified on a silicagel column
9. customfurther hydrolysis
10. customThe organic layer was separated
11. customevaporated
12. customdried
13. customresulting in 2-(2,6-difluoro-phenyl)-8-hydroxy-benzo[d][1,3]oxazin-4-one (32 mg)

ORD-Eintrag

ord-a184ea4c4a6b4c92bf8258b1217fc931

Quelldatensatz

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06180625B2