Water → 3-(4-Chloro-3-fluorophenyl)-2-propenenitrile

Diethylcyanomethyl phosphonate (3.2 ml, 18.9 mmol) was taken up in dry THF (20 ml) at 0° C. under nitrogen, and stirred as a 60% oil dispersion of NaH (756 mg, 18.9 mmol) was added portionwise over ca. 10 min. The resulting grey suspension was then stirred at 0° C. for 1 h, before a solution of 4-chloro-3-fluoro benzaldehyde (Lancaster Synthesis) (3 g, 18.9 mmol) in 5 ml THF was added dropwise. The whole reaction was then allowed to warm to room temperature over 60 h. Water (5 ml) was added, and the mixture extracted with EtOAc (3×50 ml). The combined organics were were dried (MgSO4) and evaporated to a yellow oil which was purified by column chromatography using 5% EtOAc in pentane as eluant to provide the title product as a mixture of geometric isomers (2.4 g, 70%); 1HNMR (400 MHz, CDCl3) δ: 5.82 (d, 1H), 7.19 (d, 1H), 7.23 (d, 1H), 7.30 (d, 1H), 7.42 (app.t, 1H); LRMS TS+ 199.1 (M+NH4+).

1. additionwas added portionwise over ca. 10 min
2. additionwas added dropwise
3. customThe whole reaction
4. extractionthe mixture extracted with EtOAc (3×50 ml)
5. dry with materialThe combined organics were were dried (MgSO4)
6. customevaporated to a yellow oil which
7. customwas purified by column chromatography

ORD record

ord-89072823f6a5474fb2ad74ddbe520bd4

Source dataset

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06849649B2