Methyl iodide → 2-Methyl-4-(trifluoromethoxy)benzamide

Temperatur

-30 °C

To a solution of N-Propenyl-4-trifluoromethoxy-benzamide 12 (8.0 g, 33 mmol) in THF (100 mL) at −78° C. was added n-butyllithium (29 mL, 72 mmol of a 2.5 M solution in hexanes). The reaction mixture was warmed to −30° C. for 10 min and cooled back to −78° C. A solution of MeI (2.24 mL, 33 mmol) in THF (5 mL) was slowly added to the reaction mixture. The cooling bath was removed and once the reaction temperature warmed to 0° C., 3 N HCl (10 mL) was added and the resulting two phase mixture heated to 60° C. for 1 h. Upon completion of reaction, the solution was neutralized with aqueous sodium bicarbonate and extracted with ether. The combined organic layers were dried (sodium sulfate) and concentrated. The residue was purified by ether/hexane triturated to provide the title compound (colorless solid 75%). 1H NMR (400 MHz,CDCl3) δ7.50 (d, J=8.4 Hz, 1 H, Ar), 7.09 (m, 2 H, Ar), 5.74 (broad s, 2 H, NH2), 2.52 (s, 3 H, CH3)

1. temperaturecooled back to −78° C
2. customThe cooling bath was removed
3. temperatureonce the reaction temperature warmed to 0° C.
4. addition3 N HCl (10 mL) was added
5. temperaturethe resulting two phase mixture heated to 60° C. for 1 h
6. customUpon completion of reaction
7. extractionextracted with ether
8. dry with materialThe combined organic layers were dried (sodium sulfate)
9. concentrationconcentrated
10. customThe residue was purified by ether/hexane
11. customtriturated

ORD-Eintrag

ord-63a2d7bd2d3e4a59a2f8085326f664dc

Quelldatensatz

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06376530B1