Water → HCID 19597961, compound

Temperature

-70 °C

A solution of lithium diisopropylamide in cyclohexane (5.13 mmol, 3.42 ml of a 1.5M solution) was added dropwise to a solution of (2-chlorobenzo[b]thiophen-3-yl)acetonitrile (1.06 g, 5.13 mmol) in tetrahydrofuran (10 ml) cooled to -70° C. under nitrogen. The resulting solution was stirred at -70° C. for 20 min, then a solution of 5-iodo-1,1-difluoropentane (1.2 g, 5.13 mmol) in tetrahydrofuran (5 ml) was slowly added at -70° C. The reaction mixture was stirred at -70° C. for 1 hr, then slowly allowed to warm to room temperature and left at that temperature overnight. Water (60 ml) was added to the reaction solution and the resulting mixture was extracted with ethyl acetate (3×70 ml). The combined ethyl acetate extracts were washed with brine (80 ml), dried (sodium sulfate) and concentrated in vacuo. The crude product (2.1 g) was purified by column chromatography on silica gel (200 g), eluting with 4:1 hexane/dichloromethane followed by 7:3 hexane/dichloromethane to yield the title compound as an oil (950 mg, 59% yield). 1H NMR (300 MHz, CDCl3) δ1.4-1.7 (c, 4H), 1.7-2.05 (c, 3H), 2.2 (c, 1H) 4.3 (t, 1H), 5.6, 5.78, 5.98 (3t, total 1H), 7.42 (m, 2H), 7.75 (d, 1H), 7.95 (d, 1H).

1. stirringThe reaction mixture was stirred at -70° C. for 1 hr
2. temperatureto warm to room temperature
3. waitleft at that temperature overnight
4. extractionthe resulting mixture was extracted with ethyl acetate (3×70 ml)
5. washThe combined ethyl acetate extracts were washed with brine (80 ml)
6. dry with materialdried (sodium sulfate)
7. concentrationconcentrated in vacuo
8. customThe crude product (2.1 g) was purified by column chromatography on silica gel (200 g)
9. washeluting with 4:1 hexane/dichloromethane

ORD record

ord-facf36280f624a3688bc1dbe51bd22b7

Source dataset

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06001860