Acetic Acid → 2-(4-Bromo-2-methylphenyl)-2-methylpropanenitrile

To a solution of (4-bromo-2-methyl-phenyl)-acetonitrile (1.26 g, 6 mmol) from step 3 above in DMF (15 mL) cooled to −10° C. was added a potassium t-butoxide (1.62 g, 14.4 mmol). The reaction was stirred for 15 minutes, iodomethane (0.86 mL, 13.8 mmol) was added slowly. The reaction was stirred for 2 hours then quenched with HOAc (0.51 mL, 9 mmol). The reaction mixture stirred for 20 minutes and mixed with IPE (250 mL) and water (200 mL). The layers were separated, and the aqueous layer was extracted with 3×100 mL IPE. The combined organics were washed with 200 mL water, and then dried over MgSO4. After filtering off the solids, the mother liquor was concentrated to the crude product by rotary evaporation. The residue was purified by flash column chromatography (0% to 75% EtOAc in Hexane) to give the desired product. Yield: 1.28 g, 89%. 1H NMR (400 MHz, CDCl3): δ 1.77 (6 H, s) 2.62 (3 H, s) 7.16 (1 H, d, J=8.59 Hz) 7.31–7.40 (2 H, m).

1. stirringThe reaction was stirred for 2 hours
2. stirringThe reaction mixture stirred for 20 minutes
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with 3×100 mL IPE
5. washThe combined organics were washed with 200 mL water
6. dry with materialdried over MgSO4
7. filtrationAfter filtering off the solids
8. concentrationthe mother liquor was concentrated to the crude product by rotary evaporation
9. customThe residue was purified by flash column chromatography (0% to 75% EtOAc in Hexane)

ORD record

ord-119ec2227a95483abe469b22cc57aa79

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07151105B2