Triethylamine → HCID 22037808, compound

Temperature

85 °C

A mixture of 4-phenoxyaniline (7.0 g, 37.8 mmol), bromoacetonitrile (4.5 g, 37.8 mmol) and triethylamine (4.2 g, 41.6 mmol) in tetrahydrofuran (50 mL) was heated at 85° C. for 5.25 hours then cooled and another portion of bromoacetonitrile (6.5 g, 5.46 mmol) was added. The mixture was heated at 85° C. for 18 hours then cooled and concentrated under reduced pressure. The residue was partitioned between dichloromethane (50 mL) and water (50 mL). The aqueous layer was extracted with dichloromethane (30 mL) then the combined organic solutions were extracted with 5 N aqueous sodium hydroxide (30 mL), dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel using dichloromethane/ethyl acetate (98:2) as an eluent to provide 3.8 g (45%) of the title compound as a dark brown solid: 1H NMR (DMSO-d6, 400 MHz) δ 7.32 (t, 2H), 7.03 (t, 1H), 6.87–6.94 (m, 4H), 6.76 (d, 2H), 6.26 (bs, 2H), 4.25 (s, 2H);RP-HPLC (Hypersil HS-C18, 5 μm, 100 A, 4.6×250 mm; 25%–100% acetonitrile-0.05 M ammonium acetate over 25 min, 1 mL/min) tr 18.4 min.; MS: MH+ 225.1.

1. temperaturethen cooled
2. temperatureThe mixture was heated at 85° C. for 18 hours
3. temperaturethen cooled
4. concentrationconcentrated under reduced pressure
5. customThe residue was partitioned between dichloromethane (50 mL) and water (50 mL)
6. extractionThe aqueous layer was extracted with dichloromethane (30 mL)
7. extractionthe combined organic solutions were extracted with 5 N aqueous sodium hydroxide (30 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationthe filtrate concentrated under reduced pressure
11. customThe residue was then purified by flash chromatography on silica gel

ORD record

ord-9a2b2b67968740b09716865dce6a705d

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07071199B1