Benzyl Alcohol → 2-(Benzyloxy)-4-bromo-6-fluorobenzonitrile

To a 500-mL RBF was added NaH (0.660 g, 27.5 mmol) and THF (100 mL). To this solution was added benzyl alcohol (2.385 mL, 22.94 mmol) in THF slowly via syringe, with external cooling (ice bath) when necessary. After the addition, the reaction mixture was stirred for 1 hour at room temperature. At this time, the mixture was transferred via syringe slowly to a solution of 4-bromo-2,6-difluorobenzonitrile (5 g, 22.94 mmol) in THF at 0° C. The solution was allowed to warm to room temperature and stirred over the weekend. The reaction was poured into water (50 mL), and extracted with EtOAc (3×100 mL). The organic layers were combined and dried over Na2SO4. The dried solution was filtered, and the filtrate was concentrated in vacuo to yield a pale yellow solid which was purified by flash chromatography (gradient elution 0-30% EtOAc in hexanes) to afford the title compound (3.911 g) as a white fluffy solid. 1H NMR (400 MHz, DMSO-d6): δ 5.35 (s, 2H), 7.27-7.66 (m, 7H).

1. temperaturewith external cooling (ice bath) when necessary
2. additionAfter the addition
3. temperatureto warm to room temperature
4. stirringstirred over the weekend
5. extractionextracted with EtOAc (3×100 mL)
6. dry with materialdried over Na2SO4
7. filtrationThe dried solution was filtered
8. concentrationthe filtrate was concentrated in vacuo
9. customto yield a pale yellow solid which
10. customwas purified by flash chromatography (gradient elution 0-30% EtOAc in hexanes)

ORD record

ord-08917eb3459e4e19b12ed387de120dc0

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697685B2