Ammonia → 2-Amino-4-chloro-5-methylbenzonitrile

To a solution of 2-bromo-5-chloro-4-methylaniline (13.0 g 58.96 mmol) in N-methylpyrrolidinone (100 ml) was added copper(I) cyanide (10.56 g, 118 mmol). The reaction mixture was placed in an oil bath preheated to 163° C. and stirred at this temperature for 2 h. The reaction mixture was allowed to cool to room temperature and then poured in ice-water (300 ml) and aqueous ammonia (90 ml). The brown precipitate was collected by filtration, washed with water (150 ml), dissolved in dichloromethane and the insoluble material was removed by filtration. The filtrate was washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo. Purification, on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%), afforded a white solid (6.52 g), mp 180° C.; 1H-NMR (DMSO-d6) 2.14 (s, 3H, 4-CH3), 6.11 (s, 2H, NH2), 6.86 (s, 1H, 6-H), 7.39 (s, 1H, 3-H); MS (FAB, m/z) 166,168 [(M+H)+; 90%, 40% respectively; Cl isotopic pattern]; FAB-HRMS: measured 166.0307; calculated for C8H8ClN2 (M+H)+ 166.0298.

1. customThe reaction mixture was placed in an oil bath
2. custompreheated to 163° C.
3. filtrationThe brown precipitate was collected by filtration
4. washwashed with water (150 ml)
5. dissolutiondissolved in dichloromethane
6. customthe insoluble material was removed by filtration
7. washThe filtrate was washed with brine (100 ml)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customPurification
11. washon gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%)

ORD record

ord-fd14e7fc615443658bae30f67ef9eeae

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06699861B1