Citric Acid → 2-({[3-Chloro-1-(2,6-difluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzonitrile

HRID 1867099Notes

Reaction equation

HRID 1867099 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:4]=1[C:5]#[N:6].[Cl:12][C:13]1[C:14](=[O:29])[N:15]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])[C:16]([CH3:20])=[CH:17][C:18]=1[OH:19].C([O-])([O-])=O.[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C(=O)C.C1OCCOCCOCCOCCOCCOC1>[Cl:12][C:13]1[C:14](=[O:29])[N:15]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])[C:16]([CH3:20])=[CH:17][C:18]=1[O:19][CH2:2][C:3]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:4]=1[C:5]#[N:6]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 220157702-(Bromomethyl)-5-fluorobenzonitrileHCID 547242093-chloro-1-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one

Product 1

HCID 220500172-({[3-Chloro-1-(2,6-difluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridin-4-yl]oxy}methyl)-5-fluorobenzonitrileYield 110.7%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

2-(bromomethyl)-5-fluorobenzonitrile (3.47 g, 16.2 mmol), 3-chloro-1-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one (3.15 g, 11.6 mmol), K2CO3 (2.56 g, 18.6 mmol), and 18-crown-6 (0.15 g) were dissolved in N,N-dimethylacetamide (25 mL). Reaction mixture stirred on 60° C. oil bath for 4 hours. Solvent removed by distillation. Reaction neutralized with 5% citric acid. The solid product was washed with hexane followed by 30% EtOAc/hexane. Filtered a brown solid (5.2 g, 79% yield).

Workup

  1. customReaction mixture
  2. customSolvent removed by distillation
  3. customReaction
  4. washThe solid product was washed with hexane

Sources & evidence

ORD record
ord-ebc1fdf8b8114355aca754bba547a34a
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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