1-(7-Methoxy-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethanone → 6-Isopropyl-7-methoxy-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine

Temperature

0 °C

1-(7-Methoxy-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-ethanone (10.48 g, 0.473 mol) was dissolved in 25 mL dry THF and the reaction mixture was stirred at 0° C. under nitrogen. Methyl magnesium bromide (22 mL of 3M solution in Et2O, 0.15 mol) was added dropwise, and the reaction mixture was stirred at 0° C. for two hours. The reaction was quenched by dropwise addition of 50 mL 10% aqueous ammonium chloride, followed by water. The aqueous mixture was extracted with EtOAc, and the combined organic layers were dried (MgSO4), filtered, and evaporated under reduced pressure. The residue was taken up in 95 mL acetic acid, and the reaction mixture was stirred at room temperature under nitrogen. Ammonium formate (14.92 g) and 10% Palladium on activated carbon (1.0 g) were added, and the reaction mixture was heated to 120° C. for three hours. The reaction mixture was cooled, solids were removed by filtration, and the filtrate was diluted with water, and made neutral by addition of solid sodium bicarbonate. The resulting aqueous solution was extracted with EtOAc, and the combined organic layers were dried (MgSO4), filtered, and evaporated under reduced pressure to yield 9.97 g of 6-Isopropyl-7-methoxy-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazine.

1. stirringthe reaction mixture was stirred at 0° C. for two hours
2. customThe reaction was quenched by dropwise addition of 50 mL 10% aqueous ammonium chloride
3. extractionThe aqueous mixture was extracted with EtOAc
4. dry with materialthe combined organic layers were dried (MgSO4)
5. filtrationfiltered
6. customevaporated under reduced pressure
7. stirringthe reaction mixture was stirred at room temperature under nitrogen
8. additionAmmonium formate (14.92 g) and 10% Palladium on activated carbon (1.0 g) were added
9. temperaturethe reaction mixture was heated to 120° C. for three hours
10. temperatureThe reaction mixture was cooled
11. customsolids were removed by filtration
12. additionthe filtrate was diluted with water
13. additionmade neutral by addition of solid sodium bicarbonate
14. extractionThe resulting aqueous solution was extracted with EtOAc
15. dry with materialthe combined organic layers were dried (MgSO4)
16. filtrationfiltered
17. customevaporated under reduced pressure

ORD record

ord-164c47cb233e4f058d87697c7afbdc0e

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524725B2