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

HRID 2266551Notes

Reaction equation

HRID 2266551 reaction equation
C[O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:27][CH:28]([F:30])[F:29])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.CO.O1CCCC1.[OH-].[Li+]>O>[F:30][CH:28]([F:29])[O:27][C:8]1[C:7]2[C:12](=[C:13]([F:16])[CH:14]=[CH:15][C:6]=2[O:5][CH2:4][C:3]([OH:31])=[O:2])[N:11]=[C:10]([CH2:17][CH3:18])[C:9]=1[CH2:19][C:20]1[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 68780260[4-difluoromethoxy-2-ethyl-8-fluoro-3-(4-fluorobenzyl)quinolin-5-yloxy]acetic Acid Methyl Ester

Product 1

HCID 16659922[4-difluoromethoxy-2-ethyl-8-fluoro-3-(4-fluorobenzyl)quinolin-5-yloxy]acetic Acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of [4-difluoromethoxy-2-ethyl-8-fluoro-3-(4-fluorobenzyl)quinolin-5-yloxy]acetic acid methyl ester (050 g), methanol (10 mL); tetrahydrofuran (10 mL), water (8 mL) and lithium hydroxide (0.050 g) was stirred at room temperature for 30 minutes. The mixture was partitioned between ethyl acetate and 1.0 M aqueous hydrochloric acid and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried over magnesium 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, followed by washing with diethyl ether gave title compound as a white solid, 0.090 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 extracts were dried over magnesium sulfate
  4. customthe solvent removed under reduced pressure
  5. customPurification of the residue by preparative reverse-phase
  6. customover 30 minutes
  7. washby washing with diethyl ether

Sources & evidence

ORD record
ord-901ccfba72314cf6a289b6e1f56521cc
Source dataset
uspto-grants-2010_12
Patent number
US07858640B2

Reaction notes

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