Dimethylformamide → {4-difluoromethoxy-2-ethyl-8-fluoro-3-[4-(pyrrolidine-1-carbonyl)benzyl]quinolin-5-yloxy}acetic Acid Methyl Ester

HRID 2266605Notes

Reaction equation

HRID 2266605 reaction equation
[CH3:1][O:2][C:3](=[O:34])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8](=[O:33])[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([N:28]3[CH2:32][CH2:31][CH2:30][CH2:29]3)=[O:27])=[CH:22][CH:21]=1)=[C:10]([CH2:17][CH3:18])[NH:11]2.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].Cl[C:47](OC(=O)C)([F:49])[F:48]>O>[CH3:1][O:2][C:3](=[O:34])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:33][CH:47]([F:49])[F:48])=[C:9]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([N:28]3[CH2:29][CH2:30][CH2:31][CH2:32]3)=[O:27])=[CH:24][CH:25]=1)[C:10]([CH2:17][CH3:18])=[N:11]2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 68782853{2-ethyl-8-fluoro-4-oxo-3-[4-(pyrrolidine-1-carbonyl)benzyl]-1,4-dihydroquinolin-5-yloxy}acetic Acid Methyl EsterHCID 86613376Chlorodifluoromethyl acetate

Product 1

HCID 68783388{4-difluoromethoxy-2-ethyl-8-fluoro-3-[4-(pyrrolidine-1-carbonyl)benzyl]quinolin-5-yloxy}acetic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of {2-ethyl-8-fluoro-4-oxo-3-[4-(pyrrolidine-1-carbonyl)benzyl]-1,4-dihydroquinolin-5-yloxy}acetic acid methyl ester (0.25 g), N,N-dimethylformamide (5.0 mL), potassium carbonate (0.22 g) and acetic acid chlorodifluoromethyl ester (0.28 mL) was stirred at 80° C. for 17 hours. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and the solvent removed under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and dichloromethane (1:1 by volume) gave title compound, 0.14 g.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts were dried over magnesium sulfate
  4. customthe solvent removed under reduced pressure
  5. customPurification of the residue by column chromatography on silica gel
  6. washeluting with a mixture of cyclohexane and dichloromethane (1:1 by volume)

Sources & evidence

ORD record
ord-7182c4de712b40b687af3c65a11d5307
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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