Isobutyronitrile → 2-(3-Bromo-5-fluorophenyl)-2-methylpropanenitrile

At 2-5° C. a solution of lithium bis(trimethylsilyl)amide in THF (326 ml of 1 M, 326 mmol, 1.05 equiv.) was added dropwise into a solution of 1-bromo-3,5-difluorobenzene (60 g, 311 mmol, 1.0 equiv.) and isobutyronitrile (25.8 g, 373 mmol, 1.2 equiv.) in 360 mL of THF. After stirring for 20 h, 13% starting reagent remained so an additional 0.1 eq of lithium bis(trimethylsilyl)amide was added. After an additional 6 hr, 10% starting reagent remained so another 0.1 eq. of lithium bis(trimethylsilyl)amide and 0.1 eq. of isobutyronitrile were added. The reaction mixture was stirred overnight. The reaction mixture was quenched with a 1 N HCl solution, then concentrated down to remove some of the THF. The reaction mixture was extracted with methyl-tert-butyl ether (2 times) and concentrated under reduced pressure to get the crude product (75.3 g) which was used as is.

1. additionwas added
2. waitAfter an additional 6 hr
3. additionwere added
4. stirringThe reaction mixture was stirred overnight
5. customThe reaction mixture was quenched with a 1 N HCl solution
6. concentrationconcentrated down
7. customto remove some of the THF
8. extractionThe reaction mixture was extracted with methyl-tert-butyl ether (2 times)
9. concentrationconcentrated under reduced pressure

ORD record

ord-3e7d74227a1f496ca8c5203918ba6d72

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889682B2