Hydrochloric Acid → (2-Amino-5-chloro-phenyl)-(2-methyl-pyridin-4-yl)-methanone

HRID 1497273Notes

Reaction equation

B(Cl)(Cl)Cl.[Cl:5][C:6]1[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=1.[CH3:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][N:21]=1)[C:17]#N.[Cl-].[Al+3].[Cl-].[Cl-].Cl.[OH-:27].[Na+]>ClC(Cl)C(Cl)Cl>[NH2:10][C:9]1[CH:11]=[CH:12][C:6]([Cl:5])=[CH:7][C:8]=1[C:17]([C:16]1[CH:19]=[CH:20][N:21]=[C:14]([CH3:13])[CH:15]=1)=[O:27]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of boron trichloride (9.35 ml, 9.35 mmol) in 1,1,2,2-tetrachloroethane at 0° C. was added 4-chloroaniline (1.19 g, 9.35 mmol) and the mixture was stirred for 30 minutes. 2-methyl-isonicotinonitrile (920 mg, 7.79 mmol) and aluminum chloride (1.14 g, 8.57 mmol) were added successively and the mixture was heated to reflux for 20 h. The reaction mixture was cooled to 0° C., 2N HCl (20 ml) was added and the mixture was heated to 80° C. for 30 minutes. The mixture was basified with 3N NaOH and extracted with EtOAc. The combined extracts were washed with brine, dried with Na2SO4 and evaporated. The remaining solid was purified by column chromatography (silica gel, dichloromethane/EtOAc 95:5 to 100:0) to afford the title compound (390 mg, 20%) as yellow solid. MS (ESI): 247.4 (M+H)+.

Workup

temperaturethe mixture was heated
temperatureto reflux for 20 h
temperaturethe mixture was heated to 80° C. for 30 minutes
extractionextracted with EtOAc
washThe combined extracts were washed with brine
dry with materialdried with Na2SO4
customevaporated
customThe remaining solid was purified by column chromatography (silica gel, dichloromethane/EtOAc 95:5 to 100:0)

Sources & evidence

ORD record: ord-ca58c2d88f9a4540bcf3160a6c6e2199
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199938B2

Reaction notes

Loading…