4-Fluoro-3-methoxybenzaldehyde → 1-Fluoro-2-methoxy-4-vinylbenzene

Temperature

-40 °C

To a stirred suspension of methyltriphenylphosphonium bromide (68.20 g, 0.191 mol) in anhydrous THF (400 mL) cooled to −40° C. was added n-butyllithium (2.5 M in hexanes, 71.2 mL, 0.178 mol) via syringe over 15 min, at which point the characteristic yellow color of the phosphorus ylide persisted. The reaction mixture was warmed to −10° C. over 1 h to complete the reaction. The mixture was subsequently cooled to −30° C. and a solution of 4-fluoro-3-methoxybenzaldehyde (10.00 g, 63.64 mmol) in anhydrous THF (40 mL) was added via a cannula over 10 min. The resultant mixture was warmed to ambient temperature over 16 h. The reaction was quenched by gradual addition of water (200 mL) and the aqueous extracted with diethyl ether (3×200 mL). The combined organic layers were washed with water (2×200 mL), brine (200 mL), dried (MgSO4) and concentrated under reduced pressure to give 1-fluoro-2-methoxy-4-vinylbenzene (INTERMEDIATE II.1) (8.69 g, 57.1 mmol, 90%) as a yellow oil.

1. temperatureThe reaction mixture was warmed to −10° C. over 1 h
2. customthe reaction
3. temperatureThe mixture was subsequently cooled to −30° C.
4. customThe reaction was quenched by gradual addition of water (200 mL)
5. extractionthe aqueous extracted with diethyl ether (3×200 mL)
6. washThe combined organic layers were washed with water (2×200 mL), brine (200 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated under reduced pressure

ORD record

ord-fb87ba7196964a7f8d645f5e5b7106e1

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07906504B2