Methanol → 3-Fluoro-4-methoxyphenylacetonitrile

To a suspension of t-BuOK (25.3 g, 0.207 mol) in THF (150 mL) was added a solution of TosMIC (20.3 g, 0.104 mol) in THF (50 mL) at −78° C. The mixture was stirred for 15 minutes, treated with a solution of 3-fluoro-4-methoxy-benzaldehyde (8.00 g, 51.9 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at −78° C. To the cooled reaction mixture was added methanol (50 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (200 mL). The aqueous phase was extracted with EtOAc (100 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/ethyl acetate 10:1) to afford 2-(3-fluoro-4-methoxyphenyl)acetonitrile (5.0 g, 58%). 1H NMR (400 MHz, CDCl3) δ 7.02-7.05 (m, 2H), 6.94 (t, J=8.4 Hz, 1H), 3.88 (s, 3H), 3.67 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 152.3, 147.5, 123.7, 122.5, 117.7, 115.8, 113.8, 56.3, 22.6.

1. stirringto stir for 1.5 hours at −78° C
2. customTo the cooled reaction mixture
3. temperatureThe mixture was heated
4. temperatureat reflux for 30 minutes
5. customSolvent of the reaction mixture was removed
6. customto give a crude product, which
7. extractionThe aqueous phase was extracted with EtOAc (100 mL×3)
8. customThe combined organic layers were dried
9. customevaporated under reduced pressure
10. customto give crude product, which
11. customwas purified by column chromatography (petroleum ether/ethyl acetate 10:1)

ORD record

ord-9878bdf835d64b46a2e5f0446e13c7df

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07776905B2