Cyclopentanecarbaldehyde → 3-Cyclopentylprop-2-enenitrile

A solution of diethyl cyanomethylphosphonate (7, 742.5 g, 4.2 mol, 1.1 equiv) in dry THF (5.75 L) was stirred under nitrogen on an ice-water-methanol bath and a solution of 1 M potassium tert-butoxide in THF (4 L, 4.0 mol, 1.05 equiv) was added at such a rate as to keep the temperature below 0° C. After addition of 1 M potassium tert-butoxide in THF was complete, the stirring was continued on the cold bath for 1 h and a solution of cyclopentanecarbaldehyde (6, 374 g, 3.81 mol) in dry THF (290 mL) was added at such a rate as to maintain the temperature below 0° C. The cold bath was removed, and the reaction mixture was gradually warmed to room temperature and stirred at room temperature for overnight. When the reaction was deemed complete, the reaction mixture was partitioned between methyl tent-butyl ether (MTBE, 14 L), water (10 L) and brine (6 L). The two layers were separated, and the combined organic phase was washed with brine (6 L). The aqueous phase was extracted with MTBE (10 L) and washed with brine (6 L). The combined organic extracts were concentrated under reduced pressure and the residue was distilled (65-78° C./6 torr) to afford 3-cyclopentylacrylonitrile (8, 437.8 g, 461.7 g theoretical, 94.8% yield) as a colorless oil, which was found to be a mixture of E- and Z-isomer. For 8: 1H NMR (DMSO-d6, 400 MHz, for Z-isomer) δ ppm 6.58 (t, 1H, J=10.6 Hz), 5.55 (dd, 1H, J=10.8, 0.59 Hz), 2.85 (m, 1H), 1.9-1.46 (m, 6H), 1.34 (m, 2H) and (for E-isomer) δ ppm 6.83 (q, 1H, J=8.3 Hz), 5.66 (dd, 1H, J=16.5, 1.4 Hz), 2.60 (m, 1H), 1.9-1.46 (m, 6H), 1.34 (m, 2H); 13C NMR (DMSO-d6, 100 MHz, for Z-isomer) δ ppm 159.8, 116.6, 97.7, 42.3, 32.3, 25.1 and (for E-isomer) δ ppm 160.4, 118.1, 97.9, 43.2, 31.5, 24.8; C8H11N (MW, 121.18), GCMS (EI) m/e 120 (M+−H).

1. customthe temperature below 0° C
2. temperatureto maintain the temperature below 0° C
3. customThe cold bath was removed
4. customthe reaction mixture was partitioned between methyl tent-butyl ether (MTBE, 14 L), water (10 L) and brine (6 L)
5. customThe two layers were separated
6. washthe combined organic phase was washed with brine (6 L)
7. extractionThe aqueous phase was extracted with MTBE (10 L)
8. washwashed with brine (6 L)
9. concentrationThe combined organic extracts were concentrated under reduced pressure
10. distillationthe residue was distilled (65-78° C./6 torr)

ORD record

ord-019a9bcc5d5048b0bcfe9e0a77be6cd6

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410265B2