Trimethylaluminum → 4-Chloro-1-methoxy-2-(1,1,1-trifluoro-2-methylpropan-2-YL)benzene

Temperature

-78 °C

A solution of 4-chloro-2-(2-chloro-1,1,1-trifluoropropan-2-yl)-1-methoxybenzene (C46) (derived from the preceding step, ≦4.71 mmol) in dichloromethane (30 mL) was cooled to −78° C. Trimethylaluminum (2 M in hexanes, 7.32 mL, 14.6 mmol) was then added drop-wise over a period of 10 minutes, and the reaction mixture was stirred at −78° C. for 30 minutes. It was then allowed to warm to room temperature and stirred for 16 hours, at which time it was cooled to −78° C. and quenched with water (10 mL). The reaction mixture was filtered through Celite, and the filter pad was washed with dichloromethane; the combined filtrates were washed with saturated aqueous sodium chloride solution, concentrated in vacuo, and purified using silica gel chromatography (Eluant: hexanes) to afford the product as a colorless oil. Yield: 746 mg, 2.95 mmol, 63% over 2 steps. 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 3.83 (s, 3H), 6.86 (d, J=8.8 Hz, 1H), 7.25 (dd, J=8.8, 2.6 Hz, 1H), 7.35-7.37 (m, 1H).

1. temperatureto warm to room temperature
2. stirringstirred for 16 hours, at which time it
3. temperaturewas cooled to −78° C.
4. customquenched with water (10 mL)
5. filtrationThe reaction mixture was filtered through Celite
6. washthe filter pad was washed with dichloromethane
7. washthe combined filtrates were washed with saturated aqueous sodium chloride solution
8. concentrationconcentrated in vacuo
9. custompurified

ORD record

ord-f94026652ace465891fb6fd15cb8c0ef

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067934B2