Boron tribromide → 3-Chloro-5-(4-hydroxyphenyl)isonicotinonitrile

A 1 M dichloromethane solution of boron tribromide (13.39 mL, 13.39 mmol) was added to a solution of 3-(4-(benzyloxy)phenyl)-5-chloroisonicotinonitrile (2.147 g, 6.69 mmol) in dichloromethane (20 mL) in a room temperature water bath. The orange suspension was stirred at room temperature for 40 min, poured to a stirred solution of saturated sodium bicarbonate (300 mL), diluted with dichloromethane (150 mL) and the mixture stirred overnight. The two phases were separated. The aqueous phase was extracted with dichloromethane (2×100 mL). The combined extracts were washed with saturated sodium bicarbonate (50 mL), water (2×50 mL), brine (50 mL), dried (MgSO4) and concentrated. The residue was diluted with methanol (10 mL), toluene (10 mL) and hexanes (30 mL), stirred for 1 h and filtered. The solid was rinsed with 1:3 mixture of toluene/hexanes to give 3-chloro-5-(4-hydroxyphenyl)isonicotinonitrile as tan solid (1.03 g, 65% yield). 1H NMR (400 MHz, methanol-d4) δ ppm 8.75 (1H, s), 8.71 (1H, s), 7.42-7.61 (2H, m), 6.87-7.05 (2H, m); MS (ES+) m/z: 231 (M+H); LC retention time: 3.223 min (analytical HPLC Method A).

1. stirringthe mixture stirred overnight
2. customThe two phases were separated
3. extractionThe aqueous phase was extracted with dichloromethane (2×100 mL)
4. washThe combined extracts were washed with saturated sodium bicarbonate (50 mL), water (2×50 mL), brine (50 mL)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. additionThe residue was diluted with methanol (10 mL), toluene (10 mL) and hexanes (30 mL)
8. stirringstirred for 1 h
9. filtrationfiltered
10. washThe solid was rinsed with 1:3 mixture of toluene/hexanes

ORD record

ord-92afff6210874945b31a20d435d50e65

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846673B2