Tetrahydrofuran → 4-Formyl-3-methoxybenzonitrile

Thionyl chloride (50 ml) was added to 2-methoxy-4-cyano benzoic acid (Tetrahedron Letters, 1986, 27(49), 5997–6000) (8 g, 45.2 mmol) in dichloromethane (70 ml) and the solution was refluxed for 5 h. After cooling to room temperature, the solvent was removed under reduced pressure. The crude benzoyl chloride was dissolved in diglime (120 ml), cooled at −78° C. and 1M lithium tritertbutoxyaluminium hydride in THF (46 ml, 46 mmol) was added dropwise in 3 h. Stirring was continued for 30 min at −78° C. then the reaction was allowed to reach 0° C. and quenched with water (15 ml) and 2N NaOH (15 ml). The reaction mixture was stirred for 1 h, filtered and the organic phase was removed under reduced pressure. The crude residue was purified by column chromatography eluting with n-hexane/ethyl acetate 80:20 to give 4 g of the title compound (yield 55%) as a yellow powder, mp=112–114° C.

1. temperaturethe solution was refluxed for 5 h
2. customthe solvent was removed under reduced pressure
3. dissolutionThe crude benzoyl chloride was dissolved in diglime (120 ml)
4. temperaturecooled at −78° C.
5. customto reach 0° C.
6. customquenched with water (15 ml) and 2N NaOH (15 ml)
7. stirringThe reaction mixture was stirred for 1 h
8. filtrationfiltered
9. customthe organic phase was removed under reduced pressure
10. customThe crude residue was purified by column chromatography
11. washeluting with n-hexane/ethyl acetate 80:20

ORD record

ord-df8059d25d9c4602965582915bb6793d

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07220769B2