Ethyl ketone → 3-(2-Bromo-5-methylphenyl)pentan-3-ol

Temperature

-10 °C

To a solution of 1-bromo-2-iodo-4-methylbenzene (28 g, 94 mmol) in THF (10 ml) at −10° C. under nitrogen was slowly added i-PrMgBr (47 ml, 94 mmol). The reaction mixture was stirred for 1 h at −10° C. Then the reaction mixture was cooled to −30° C., and pentan-3-one (8.1 g, 94 mmol) was added dropwise. The reaction mixture was stirred for 1 h at −30° C. under nitrogen and then warmed to rt and stirred for additional 2 h. Then the reaction mixture was quenched with 2N HCl solution and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (10:0 to 5:1) to give the desired compound (6.5 g, yield 26.9%) as colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.52-7.50 (d, 1H), 7.43-7.40 (d, 1H), 6.95-6.92 (d, 1H), 2.48-2.40 (q, 2H), 2.31 (s, 3H), 1.86-1.78 (q, 2H), 0.77-0.71 (m, 6H). MS: m/z=257 and 259 [M+1]+.

1. customat −10° C.
2. temperatureThen the reaction mixture was cooled to −30° C.
3. stirringThe reaction mixture was stirred for 1 h at −30° C. under nitrogen
4. temperaturewarmed to rt
5. stirringstirred for additional 2 h
6. customThen the reaction mixture was quenched with 2N HCl solution
7. extractionextracted with EA
8. washThe combined organic layers were washed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by column chromatography over silica gel
13. washeluted with PE

ORD record

ord-d1d551ecfc6b458685f4f85ef234a2b0

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853186B2