Acetic Acid → HCID 25095561, compound

HRID 1944281Notes

Reaction equation

HRID 1944281 reaction equation
C[O:2][C:3](=[O:35])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:31][CH:32]([F:34])[F:33])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]3[O:27][CH:28]=[CH:29][N:30]=3)=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.[OH-].[Li+].C(O)(=O)C>CO.O>[F:34][CH:32]([F:33])[O:31][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:35])=[O:2])[N:11]=[C:10]([CH2:17][CH3:18])[C:9]=1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:27][CH:28]=[CH:29][N:30]=2)=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 67456423HCID 67456423, compound

Product 1

HCID 25095561HCID 25095561, compoundYield 11.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A solution of [4-difluoromethoxy-2-ethyl-8-fluoro-3-(4-oxazol-2-ylbenzyl)quinolin-5-yloxy]acetic acid methyl ester (0.73 g) in methanol (6.0 mL) and water (0.6 mL) was treated with 5.0 M aqueous lithium hydroxide solution (0.30 mL), and the resulting mixture was stirred at room temperature for 2 hours. The mixture was acidified by the addition of glacial acetic acid, concentrated under reduced pressure, and the residue partitioned between ethyl acetate and water. The organic phase was dried over magnesium sulfate, concentrated under reduced pressure, and then diluted with acetonitrile. The resulting precipitate was removed by filtration, washed with acetonitrile, and the filtrate concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and glacial acetic acid (50:1:1 to 10:1:1 by volume). Further purification by preparative reverse-phase HPLC, and then column chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and glacial acetic acid (40:1:0.1 to 20:1:0.1 by volume) gave title compound as a white solid (0.082 g).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customthe residue partitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additiondiluted with acetonitrile
  6. customThe resulting precipitate was removed by filtration
  7. washwashed with acetonitrile
  8. concentrationthe filtrate concentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel
  10. washeluting with a mixture of dichloromethane, methanol and glacial acetic acid (50:1:1 to 10:1:1 by volume)
  11. customFurther purification by preparative reverse-phase HPLC
  12. washcolumn chromatography on silica gel, eluting with a mixture of dichloromethane, methanol and glacial acetic acid (40:1:0.1 to 20:1:0.1 by volume)

Sources & evidence

ORD record
ord-081a46b38f45487ea89f3406c879b3cc
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

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