Hydrochloric Acid → 1-[2-[(7,8-Difluoro-2-methyl-3-quinolinyl)oxy]-6-fluorophenyl]ethanone

HRID 1618908Notes

Reaction equation

HRID 1618908 reaction equation
[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[C:7]([OH:14])[C:8]([CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:15][C:16]([C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1F)=[O:17].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[F:24][C:23]1[CH:22]=[CH:21][CH:20]=[C:19]([O:14][C:7]2[C:8]([CH3:13])=[N:9][C:10]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([F:1])[C:11]=3[F:12])[C:18]=1[C:16](=[O:17])[CH3:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 836431-(2,6-Difluorophenyl)ethan-1-oneHCID 682878637,8-Difluoro-2-methylquinolin-3-ol

Product 1

HCID 682890471-[2-[(7,8-Difluoro-2-methyl-3-quinolinyl)oxy]-6-fluorophenyl]ethanoneYield 38.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

26.3 g of 7,8-difluoro-3-hydroxy-2-methylquinoline was dissolved in 200 mL of dimethylformamide. 27.2 g of 2,6-difluoroacetophenone and 24.0 g of potassium carbonate were added to the solution and the mixture was stirred for 4 hours at 100° C. After the thus obtained reaction solution was poured into ice water, and neutralized with dilute hydrochloric acid, the liquid was separated with ethyl acetate. The organic layer was concentrated and purified by silica gel column chromatography to obtain 17.0 g of 1-[2-fluoro-6-(7,8-difluoro-2-methylquinolin-3-yloxy)-phenyl]-ethanone.

Workup

  1. customAfter the thus obtained reaction solution
  2. customthe liquid was separated with ethyl acetate
  3. concentrationThe organic layer was concentrated
  4. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-3d1d993ed0bc45488aece1e1a4f75ddb
Source dataset
uspto-grants-2014_07
Patent number
US08772200B2

Reaction notes

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