Methanol → [2-difluoromethoxy-8-fluoro-3-(4-fluorobenzyl)-4-methylquinolin-5-yloxy]acetic Acid

HRID 2266557Notes

Reaction equation

HRID 2266557 reaction equation
C[O:2][C:3](=[O:30])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:29])=[C:9]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)[C:10]([O:17][CH:18]([F:20])[F:19])=[N:11]2.O1CCCC1.CO.[OH-].[Li+]>O>[F:20][CH:18]([F:19])[O:17][C:10]1[C:9]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)=[C:8]([CH3:29])[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:30])=[O:2])[N:11]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 68786070[2-difluoromethoxy-8-fluoro-3-(4-fluorobenzyl)-4-methylquinolin-5-yloxy]acetic Acid Methyl Ester

Product 1

HCID 57742512[2-difluoromethoxy-8-fluoro-3-(4-fluorobenzyl)-4-methylquinolin-5-yloxy]acetic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of [2-difluoromethoxy-8-fluoro-3-(4-fluorobenzyl)-4-methylquinolin-5-yloxy]acetic acid methyl ester (0.20 g), tetrahydrofuran (4.0 mL), methanol (4.0 mL), water (3.0 mL) and lithium hydroxide (0.020 g) was stirred at room temperature for 40 minutes. The mixture was partitioned between ethyl acetate and 1.0 M aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate and the solvent removed under reduced pressure. Purification of the residue by preparative reverse-phase HPLC using a gradient over 30 minutes of acetonitrile in water gave title compound as a white solid, 0.10 g.

Workup

  1. customThe mixture was partitioned between ethyl acetate and 1.0 M aqueous hydrochloric acid
  2. extractionThe aqueous phase was extracted with ethyl acetate
  3. dry with materialthe combined organic phases were dried over sodium sulfate
  4. customthe solvent removed under reduced pressure
  5. customPurification of the residue by preparative reverse-phase
  6. customover 30 minutes

Sources & evidence

ORD record
ord-1303acc1dcdd4731a2c050f9708a754c
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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