Potassium Carbonate → 3-Chloro-5-[(6-methyl-2-oxo-1,2-dihydropyridin-4-yl)oxy]benzonitrile

HRID 1952340Notes

Reaction equation

[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[CH:3]=1.[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[C:17](F)[CH:18]=1)[C:14]#[N:15].C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1>[Cl:10][C:11]1[CH:12]=[C:13]([CH:16]=[C:17]([O:1][C:2]2[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[CH:3]=2)[CH:18]=1)[C:14]#[N:15]

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 4-hydroxy-6-methyl-2-oxo-1,2-dihydropyridine (3-2; 20.1 g; 161 mmol) in NMP (1.6 L) was added 3-chloro-5-fluorobenzonitrile (3-1; 25 g; 161 mmol) and potassium carbonate (44.4 g; 321 mmol). The resulting solution stirred at 120° C. overnight. The reaction mixture was cooled to ambient temperature and diluted with 4 L of ice-water. The aqueous layer was acidified to pH 5 to precipitate out the product. The precipitate was collected via filtration, washed with water, and air dried. The crude solid product was triturated in 5% methanol/dichloromethane and filtered to give a solid. The solid was triturated with 1:1 ethyl acetate:hexane, stirred, and filtered to afford the title product as a tan solid. MS M+1=261.0.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
customto precipitate out the product
filtrationThe precipitate was collected via filtration
washwashed with water, and air
customdried
customThe crude solid product was triturated in 5% methanol/dichloromethane
filtrationfiltered
customto give a solid
customThe solid was triturated with 1:1 ethyl acetate
stirringhexane, stirred
filtrationfiltered

Sources & evidence

ORD record: ord-3263742d800345689918d641e5038187
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404856B2

Reaction notes

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