1-(Bromomethyl)-3-phenoxybenzene → 1-[(2E)-4-(4-Chlorophenyl)-2,3-difluoro-6-methoxy-2-hexenyl]-3-phenoxybenzene

To a stirred solution of 1-chloro-4-[(2E)-2,3-difluoro-1-(2-methoxyethyl)-2-propenyl]benzene (0.87 g, 3.52 mmol) in tetrahydrofuran (10 ml) under nitrogen at −65° C. was added n-butyllithium (1.1 ml of a 2.5 M solution in hexane, 2.75 mmol). To this mixture was added zinc chloride (5.3 ml of 0.5 M in tetrahydrofuran, 2.65 mmol) and the resulting mixture was stirred for one hour. Tetrakis(triphenyl-phosphine)palladium (0.066 g, 0.057 mmol) in tetrahydrofuran (1 ml) was added, followed by α-bromo-3-phenoxytoluene (0.70 g, 2.66 mmol) in tetrahydrofuran (2 ml), and the resulting mixture was stirred and allowed to warm to room temperature over four hours and was then stirred for another sixteen hours. The reaction mixture was then quenched with water, diluted with 10% hydrochloric acid and thoroughly extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to a brown oil (1.378 g). Chromatography of this oil on silica gel eluting with ethyl acetate:hexane (5:95) afforded the title compound as a yellow syrup (0.359 g) which was characterized by IR, 1HNMR, 19FNMR and mass spectral analysis.

1. stirringthe resulting mixture was stirred
2. stirringwas then stirred for another sixteen hours
3. customThe reaction mixture was then quenched with water
4. additiondiluted with 10% hydrochloric acid
5. extractionthoroughly extracted with ethyl acetate
6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
7. concentrationconcentrated in vacuo to a brown oil (1.378 g)

ORD record

ord-af702b7b7fb5417084c922ed900ce447

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06506800B2