Methoxymethyl-triphenylphosphonium chloride → 5-Chloro-2-(2-methoxyvinyl)-benzoic acid

Temperature

0 °C

To a cooled (0° C.) slurry of methoxymethyltriphenylphosphonium chloride (39 g) in a mixture of diethyl ether (200 ml) and tert-butanol (50 ml) was added potassium tert-butoxide (12.8 g) portion wise. The resulting mixture was stirred at 0° C. for 1 hour, then a solution of 2-formyl-5-chlorobenzoic acid (prepared as described in J. Org. Chem. 61, 3402 (1996)) (10 g) in diethyl ether (50 ml) was added dropwise over 15 minutes. The resulting mixture was stirred for 1 hour at 0° C., then warmed to ambient and stirred for an additional 90 minutes. The mixture was diluted with water (200 ml) and the organic phase removed. The aqueous phase was acidified to pH 1 with 1M HCl and extracted with ethyl acetate (3×50 ml). The combined extracts were washed with brine, dried (magnesium sulfate), filtered and concentrated. The residue was purified by flash chromatography (50% ethyl acetate/hexane) to afford the sub-title compound as a yellow solid (9.13 g, 80%). 1H NMR (400 MHz, CDCl3) δ 3.70-3.81 (3H, s), 6.20 (0.3H, d, cis alkene), 6.30 (0.3H, d, cis alkene), 6.80 (0.7H, d, trans alkene), 7.01 (0.7H, d, trans alkene), 7.30-8.15 (3H, m) ppm.

1. stirringThe resulting mixture was stirred for 1 hour at 0° C.
2. temperaturewarmed
3. stirringstirred for an additional 90 minutes
4. customthe organic phase removed
5. extractionextracted with ethyl acetate (3×50 ml)
6. washThe combined extracts were washed with brine
7. dry with materialdried (magnesium sulfate)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography (50% ethyl acetate/hexane)

ORD record

ord-db35868129e14ccd9cf290ef443b136e

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129381B2