Water → 1-(4-Bromophenyl)cyclobutanecarbonitrile

Temperature

100 °C

KOH (11.4 g, 204 mmol, 8 eq), water (3.75 mL), 4-bromophenylacetonitrile (5.00 g, 25.5 mmol, 1.0 eq), 1,3-dibromopropane (5.15 g, 25.5 mmol, 1.0 eq), tetrabutylammonium bromide (82 mg, 0.26 mmol, 0.01 eq), and toluene (68 mL) were slowly stirred while heating to 100° C. The biphasic reaction was kept at 100° C. for 30 minutes. The heat was removed, the reaction was slightly cooled, the stirring was then increased to rapid, and then heating continued up to reflux, 115° C. After 1.5 hours at 115° C., the reaction was cooled, diluted with water, and extracted with EtOAc (×3). The combined organics were dried with brine and Na2SO4, and then concentrated in vacuo onto Celite. The resulting material was purified by silica gel chromatography by eluting with a gradient of heptane and EtOAc (0% to 35% EtOAc) to provide Compound [CXXXIV]: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.99-2.15 (m, J=11.52, 9.02, 9.02, 4.40, 4.40 Hz, 1H) 2.34-2.51 (m, 1H) 2.51-2.65 (m, 2H) 2.74-2.89 (m, 2H) 7.21-7.36 (m, 2H) 7.45-7.57 (m, 2H).

1. customThe biphasic reaction
2. customThe heat was removed
3. temperaturethe reaction was slightly cooled
4. temperaturethe stirring was then increased to rapid, and
5. temperaturethen heating
6. temperatureto reflux, 115° C
7. waitAfter 1.5 hours at 115° C.
8. temperaturethe reaction was cooled
9. additiondiluted with water
10. extractionextracted with EtOAc (×3)
11. dry with materialThe combined organics were dried with brine and Na2SO4
12. concentrationconcentrated in vacuo onto Celite
13. customThe resulting material was purified by silica gel chromatography
14. washby eluting with a gradient of heptane and EtOAc (0% to 35% EtOAc)
15. customto provide Compound [CXXXIV]

ORD record

ord-a537afc5e58d4fa9a5a6c68c074843a9

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614221B2