Ammonium Chloride → 4-Bromo-1-fluoro-2-(2-methoxyethenyl)benzene

Potassium tert-butoxide (1.2 molar equivalents) was added portionwise, over 30 minutes, to a stirred suspension of (methoxymethyl)triphenylphosphonium chloride (1.3 molar equivalents) in THF (2.5 volumes) at −3° C. (+ or −2° C.). A deep red colour developed. The temperature was ramped to 18° C. over 0.5 hour and the reaction stirred for a further 1.5 hours. 5-Bromo-2-fluorobenzaldehyde (limiting reagent) as a solution in THF (5 volumes) was then added over 90 minutes, such that the temperature of the reaction did not exceed 24° C. The reaction was then stirred for 2 hours at room temperature. The reaction mixture was poured into saturated aqueous ammonium chloride solution (10 volumes) and extracted with t-BME (2×2.5 volumes). The combined extracts were washed with brine (3×2 volumes), dried (Na2SO4), filtered and evaporated in vacuo. The oily residue was extracted with iso-hexane (8×0.5 volumes). Combined iso-hexane extracts were filtered, then washed with glacial acetic acid (2 volumes) and 50% glacial acetic acid in water (2 volumes). After drying (Na2SO4) and filtering, the solvent was removed on a rotary evaporator to give a pale orange oil. Yield was 90% of theoretical.

1. customdid not exceed 24° C
2. stirringThe reaction was then stirred for 2 hours at room temperature
3. extractionextracted with t-BME (2×2.5 volumes)
4. washThe combined extracts were washed with brine (3×2 volumes)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. extractionThe oily residue was extracted with iso-hexane (8×0.5 volumes)
9. filtrationCombined iso-hexane extracts were filtered
10. washwashed with glacial acetic acid (2 volumes) and 50% glacial acetic acid in water (2 volumes)
11. dry with materialAfter drying (Na2SO4)
12. filtrationfiltering
13. customthe solvent was removed on a rotary evaporator
14. customto give a pale orange oil

ORD record

ord-a6dd1efc32b54e43b1297821218456ab

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148373B2