Phenol → 4-Phenoxybenzonitrile

Temperature

90 °C

To phenol (1.23 g, 13.10 mmol), copper(I) iodide (333 mg, 1.75 mmol), cesium carbonate (5.69 g, 17.47 mmol), 4-iodobenzonitrile (2.00 g, 8.73 mmol) and N,N-dimethylglycine hydrochloride (366 mg, 2.62 mmol) under nitrogen was added degassed 1,4-dioxane (10.0 mL). The whole mixture was heated at 90° C. for 88 hours. The cooled mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layers were combined and washed with brine (100 mL) and dried with Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography EtOAc/Hex (1:12→1:8) to give the pure product as a white solid (quantitative yield). 1H NMR (300 MHz, CDCL3) δ(ppm): 7.00 (2H, d, J=9.1 Hz), 7.06 (2H, d, J=7.6 Hz), 7.23 (1H, t, J=7.2Hz), 7.41 (2H, t, J=8.1 Hz), 7.59 (2H, d, J=9.1 Hz). 13C NMR (75 MHz, CDCL3) δ(ppm): 105.9, 118.0 (CH), 119.0, 120.5 (CH), 125.3 (CH), 130.4 (CH), 134.2 (CH), 154.9, 161.8. MS (FAB+): 196 (MH+). HRMS for C13H9NO (MH+): calculated: 196.0762; found 196.0780.

1. customdegassed 1,4-dioxane (10.0 mL)
2. customThe cooled mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
5. washwashed with brine (100 mL)
6. dry with materialdried with Na2SO4
7. concentrationconcentrated in vacuo
8. customThe crude material was purified by column chromatography EtOAc/Hex (1:12→1:8)

ORD record

ord-d45c3cb81bd34535946635f50d74fc73

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045442B2