Ethyl 4,4,4-trifluoroacetoacetate → 8-trifluoromethyl-3,4-dihydro-2H,5H-1-oxa-4,5-diaza-anthracen-6-one

To a solution of 3,4-dihydro-2H-benzo[1,4]oxazin-6-yl amine (0.56 g, 3.73 mmol) in toluene (20 mL) was added ethyl 4,4,4-trifluoroacetoacetate (0.55 mL, 3.73 mmol) and 4 drops of pyridine. The solution was heated to reflux for 6 hours, then allowed to stir overnight at room temperature. The solvent was removed under vacuum and the residue triturated with diethyl ether. The solid was filtered off and washed with diethyl ether to yield a gray solid which was determined by 1HNMR to contain crude N-(3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,4,4-trifluoro-3-oxo-butyramide. The rest of the material in the filtrate was also determined by 1HNMR to be crude N-(3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,4,4-trifluoro-3-oxo-butyramide, but much less pure than the gray solid filtered off. The mixture was recovered by evaporating the ether. This mixture (0.8 g) was stirred in of concentrated sulfuric acid (8 mL) overnight at room temperature. The reaction mixture was then poured onto ice and neutralized by adding 1N sodium carbonate. The resulting solution was extracted three times with ethyl acetate, the extracts dried over magnesium sulfate, filtered and evaporated under vacuum to yield a brown oil. The brown oil (crude material) was purified by column chromatography on a Biotage system eluting with 4% methanol/ethyl acetate to yield 8-trifluoromethyl-3,4-dihydro-2H,5H-1-oxa-4,5diaza-anthracen-6-one as the main product.

1. temperatureThe solution was heated
2. temperatureto reflux for 6 hours
3. customThe solvent was removed under vacuum
4. customthe residue triturated with diethyl ether
5. filtrationThe solid was filtered off
6. washwashed with diethyl ether
7. customto yield a gray solid which
8. filtrationmuch less pure than the gray solid filtered off
9. customThe mixture was recovered
10. customby evaporating the ether
11. stirringThis mixture (0.8 g) was stirred in of concentrated sulfuric acid (8 mL) overnight at room temperature
12. additionThe reaction mixture was then poured onto ice
13. additionby adding 1N sodium carbonate
14. extractionThe resulting solution was extracted three times with ethyl acetate
15. dry with materialthe extracts dried over magnesium sulfate
16. filtrationfiltered
17. customevaporated under vacuum
18. customto yield a brown oil
19. customThe brown oil (crude material) was purified by column chromatography on a Biotage system
20. washeluting with 4% methanol/ethyl acetate

ORD 기록

ord-c8cdc9c0ab8746b28bf6698f3a971bb6

출처 데이터셋

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06858621B2