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

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.

1. customThe crude reaction mixture
2. customwas then separated
3. extractionthe aqueous fraction extracted twice with EtOAc
4. dry with materialThe combined EtOAc extracts were dried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification by silica gel column chromatography (eluent: 10% to 20% gradient of EtOAc in hexane)
8. customafforded trans-86 (0.3 g) as an yellow liquid

ORD record

ord-454c626f5e5349dc92f2c09969e268a4

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07635695B2