Sodium hydride → 6-(3-[4-(5-Cyanopentyloxy)phenyl]propoxy}hexanenitrile

Temperature

80 °C

A solution of 3-(4-hydroxyphenyl)-1-propanol (2.0 g, 13.1 mmole) in DMF (5 mL) was added to a solution of DMF (35 mL) containing NaH (1.31 g, 60% in mineral oil) at 0° C. under nitrogen atmosphere. The reaction mixture was slowly warmed to 80° C. After stirring for 1 h at 80° C., the reaction mixture was cooled to 0° C., and 6-bromohexanenitrile (5.78 g, 32.83 mmole) was added. The final mixture was re-heated to 80° C., and stirred for 24 h. The reaction mixture was quenched with saturated NaCl solution (200 mL), and the product was extracted with EtOAc (300 mL). The organic layer was washed with brine solution, dried with Na2SO4, and evaporated to dryness, yielding a pale yellow solid. Purification of the crude product by flash silica column chromatography: 4/1 to 1/1 hexane/EtOAc provided 6-{3-[4-(5-cyanopentyloxy)phenyl]propoxy}hexanenitrile in 30% yield (1.33 g). Rf=0.63 in 111 EtOAc/hexane. 1H-NMR (CDCl3, 299.96 MHz): δ (ppm) 7.09-7.07 (d, 2H), 6.81-6.78 (d, 2H), 3.96-3.92 (t, 2H), 3.42-3.37 (m, 4H), 2.64-2.58 (t, 2H), 2.39-2.32 (m, 4H), 1.87-1.52 (m, 14H).

1. temperaturethe reaction mixture was cooled to 0° C.
2. stirringstirred for 24 h
3. customThe reaction mixture was quenched with saturated NaCl solution (200 mL)
4. extractionthe product was extracted with EtOAc (300 mL)
5. washThe organic layer was washed with brine solution
6. dry with materialdried with Na2SO4
7. customevaporated to dryness
8. customyielding a pale yellow solid
9. customPurification of the crude product by flash silica column chromatography

ORD record

ord-39ffc8392d15474e973b40ad430c14ca

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06713651B1