Ammonium Chloride → 4-Isobutyl-dihydro-furan-2-one

Temperature

-40 °C

Cyanide 3 (0.86 g, 7.1 mmol) in THF (30 mL) was added dropwise over 1 hour to a stirring mixture of lithium hexamethyldisilazide (7.8 mL of a 1 M solution in THF, 7.8 mmol) in THF (40 mL) at −78° C. under argon. The mixture was allowed to warm to −40° C. and stirred for 2 hours. The mixture was cooled to −78° C. and dimethylallyl bromide (1.3 mL, 10.6 mmol) was added. The mixture was stirred for a further 2 hours at −78° C. and then allowed to warm to room temperature overnight. Saturated ammonium chloride solution (20 mL) was added, and the mixture was diluted with ether (50 mL) and dilute hydrochloric acid (30 mL). The aqueous layer was further extracted with ether (2×50 mL), and the combined 15 organic fractions were washed with brine, dried (MgSO4), and the solvent was evaporated under reduced pressure. The residue was chromatographed (SiO2, heptane-ethyl acetate, 98:2) to give the cyanoalkene 4 (0.96 g, 72%) as a colorless oil; Rf(heptane-ethyl acetate, 95:5) 0.38; νmax(film)/cm−1 2230 (CN),1673 (C═C); δH (400 MHz; CDCl3) 5.27 (1H, tt, J 7.6, 1.3, CHCMe2), 2.89 (2H, m), 2.30–2.22 (4H, m), 2.10 (2H, d, J 14.2), 1.94 (2H, m), 1.84–1.62 (2H, m), 1.65 (3 H, s, Me), 1.55 (3H, s, Me); m/z (AP+) 190 (M+H, 100%).

1. temperatureThe mixture was cooled to −78° C.
2. stirringThe mixture was stirred for a further 2 hours at −78° C.
3. temperatureto warm to room temperature overnight
4. extractionThe aqueous layer was further extracted with ether (2×50 mL)
5. washwere washed with brine
6. dry with materialdried (MgSO4)
7. customthe solvent was evaporated under reduced pressure
8. customThe residue was chromatographed (SiO2, heptane-ethyl acetate, 98:2)

ORD record

ord-0e827b1bd27e4ac6b6ec3b9662839883

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07189747B2