Methanol → 2-(3-Chloro-4-methoxyphenyl)acetonitrile

Temperature

-78 °C

To a suspension of potassium tert-butoxide (2.36 g, 20 mmol, 4 eq.) in THF (15 mL), a solution of tosylmethyl isocyanide (1.95 g, 10 mmol, 2 eq.) in THF (5 mL) was added at −78° C. The mixture was stirred at −78° C. for 15 min. A solution of 3-chloro-4-methoxybenzaldehyde (879 mg, 5 mmol, 1 eq.) in THF (5 mL) was added dropwise. The resulting mixture was stirred for 1.5 hours at −78° C. To the cooled reaction mixture, methanol (5 mL) was added. The mixture was then heated at reflux for 30 min. The solvent was removed in vacuo. The residue was partitioned between water (20 mL) and AcOEt (10 mL). The aq. phase was extracted with AcOEt (2×10 mL). The comb. org. layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 50 fractions of 45 mL, Heptane to Heptane+25% AcOEt) to yield (3-chloro-4-methoxy-phenyl)-acetonitrile as a pale yellow oil that solidified upon standing.

1. stirringThe resulting mixture was stirred for 1.5 hours at −78° C
2. additionwas added
3. temperatureThe mixture was then heated
4. temperatureat reflux for 30 min
5. customThe solvent was removed in vacuo
6. customThe residue was partitioned between water (20 mL) and AcOEt (10 mL)
7. extractionThe aq. phase was extracted with AcOEt (2×10 mL)
8. dry with materiallayers were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 50 fractions of 45 mL, Heptane to Heptane+25% AcOEt)

ORD record

ord-f3426f44c8644ed4948a643cc1c37c2d

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09255090B2