Dimethylamine → 1-[3-bromo-5-(trifluoromethyl)phenyl]-N,N-dimethylmethanamine

To a solution of 3-bromo-5-(trifluoromethyl)benzaldehyde (2.0 g, 7.9 mmol, Combi-blocks) in methylene chloride (10 mL) was added a solution of 2.0M dimethylamine in tetrahydrofuran (7.9 mL, 16 mmol) and the reaction was stirred for 15 minutes at room temperature. The reaction was then cooled to 0° C. and sodium triacetoxyborohydride (2.5 g, 12 mmol) was added. The resulting mixture was warmed to room temperature and was stirred for 24 hours. The solvents were removed in vacuo. Saturated sodium bicarbonate solution was added and the resulting mixture was extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel column chromatography, eluting with a gradient from 10-40% ethyl acetate in hexanes afforded product as a colorless oil (1.58 g, 71%). 1H NMR (300 MHz, CDCl3) δ 7.68 (s, 1H), 7.65 (s, 1H), 7.57-7.46 (m, 1H), 3.45 (s, 2H), 2.25 (s, 6H); 19F NMR (282 MHz, CDCl3) δ−63.10 (s); LCMS (M+H)+: 282.0, 284.0.

1. temperatureThe reaction was then cooled to 0° C.
2. temperatureThe resulting mixture was warmed to room temperature
3. stirringwas stirred for 24 hours
4. customThe solvents were removed in vacuo
5. additionSaturated sodium bicarbonate solution was added
6. extractionthe resulting mixture was extracted three times with ethyl acetate
7. washThe combined organic extracts were washed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by silica gel column chromatography
12. washeluting with a gradient from 10-40% ethyl acetate in hexanes afforded product as a colorless oil (1.58 g, 71%)

ORD record

ord-fd9dbcd6ddb448919a669d79666231a1

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933085B2