Hydrochloric Acid → 3-Chloro-5-hydroxybenzonitrile

Temperature

185 °C

3-Chloro-5-(methyloxy)benzonitrile (46.48 g, 277 mmol) and anhydrous Lil (60.77 g, 454.4 mmol) were suspended in anhydrous 2,4,6-collidine (200 mL) under nitrogen and heated to 185° C. for 8 h. The reaction mixture was cooled to RT and solidified upon standing. The solid was broken-up and added to a mixture of 10% HCl and ice. The solution was extracted with EtOAc (3×200 mL), dried over MgSO4 and evaporated. The solid was triturated in hexanes and EtOAc to afford an off-white solid and a second crop of product was obtained from the filtrate. The combined material was dried under vacuum to afford the title compound (32.40 g, 76%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 10.69 (s, 1H), 7.37 (t, 1H), 7.09-7.13 (m, 2H). MS: m/z 152.1 (M−1).

1. temperatureThe reaction mixture was cooled to RT
2. extractionThe solution was extracted with EtOAc (3×200 mL)
3. dry with materialdried over MgSO4
4. customevaporated
5. customThe solid was triturated in hexanes
6. customEtOAc to afford an off-white solid
7. customa second crop of product was obtained from the filtrate
8. customThe combined material was dried under vacuum

ORD record

ord-7b7f8a0097aa40c2b857f3c5aae33705

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304419B2