4-Chlorobutyronitrile → 2-(4-Bromo-thiophen-2-yl)-tetrahydro-furan-3-carbonitrile

Participants

Reaction Steps

Addition of 4-bromo-2-thiophenecarboxaldehyde 63 (Aldrich, Wis.) (1.0 g, 5.23 mmol) to a solution of t-BuOK (1 M in THF, 5.23 mL, 5.23 mmol) at 0° C. was followed immediately by the addition of 4-chloro-butyronitrile (0.51 mL, 5.3 mmol). After 3 h, the reaction mixture was allowed to warm to the room temperature and saturated, aqueous NH4Cl solution was then added. The crude reaction mixture was then separated and the aqueous fraction extracted twice with EtOAc. The combined EtOAc extracts were dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel column chromatography (eluent: 10% to 20% gradient of EtOAc in hexane) afforded trans-86 (0.3 g) as an yellow liquid. 1H NMR (400 MHz, d6-DMSO) δ: 7.68 (d, J=1.5 Hz, 1H), 7.19 (dd, J=1.0 Hz and 1.5 Hz, 1H), 5.26 (d, J=7.0 Hz, 1H), 4.04 (m, 1H), 3.96 (m, 1H), 3.44 (m, 1H), 2.41 (m, 1H), 2.29 (m, 1H). MS (EI) m/z [(M+H+)+ (79Br)] 258 and [(M+H+)+ (81Br)] 260.

Provenance & Evidence