Methanol → 2-Cyano-3-{4-[2-(4-hydroxyphenyl)ethoxy]phenyl}-acrylic acid

HRID 987233Notes

Reaction equation

HRID 987233 reaction equation
C([O:3][C:4](=[O:29])[C:5]([C:27]#[N:28])=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][S:23]([CH3:26])(=[O:25])=[O:24])=[CH:18][CH:17]=2)=[CH:9][CH:8]=1)C.[OH-].[Li+].CO>O>[C:27]([C:5](=[CH:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][S:23]([CH3:26])(=[O:25])=[O:24])=[CH:18][CH:17]=2)=[CH:11][CH:12]=1)[C:4]([OH:29])=[O:3])#[N:28].[C:27]([C:5](=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=2)=[CH:9][CH:8]=1)[C:4]([OH:29])=[O:3])#[N:28]

Participants

6

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 865950572-Cyano-3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]phenyl}acrylic acid ethyl ester

Product 2

HCID 696292652-Cyano-3-{4-[2-(4-hydroxyphenyl)ethoxy]phenyl}-acrylic acidHCID 865950582-Cyano-3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]-phenyl}acrylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

2-Cyano-3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]phenyl}acrylic acid ethyl ester (described in Example 6) (0.201 g; 0.483 mmole), lithium hydroxide (0.04 g; 1.67 mmole), methanol (2.3 ml) and water (2.3 ml) was stirred at 40° C. for 23 hours. More water was added, methanol was removed by evaporation in vacuo and the mixture was acidified using potassium hydrogen sulfate. The mixture was extracted with ethyl acetate and the organic phase was dried (sodium sulfate), filtered and evaporated in vacuo. The crude products were purified on preparative HPLC using acetonitrile (gradient 30-60%): ammonium acetate (0.1 M). The fractions were acidified with potassium hydrogen sulfate and then extracted with ethyl acetate. The organic phases were combined and evaporated in vacuo to give 7 mg of 2-cyano-3-{4-[2-(4-methanesulfonyloxyphenyl)ethoxy]-phenyl}acrylic acid and 21,8 mg of 2-cyano-3-{4-[2-(4-hydroxyphenyl)ethoxy]phenyl}-acrylic acid.

Workup

  1. custommethanol was removed by evaporation in vacuo
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialthe organic phase was dried (sodium sulfate)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude products were purified on preparative HPLC
  7. extractionextracted with ethyl acetate
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-0b325fc0d41f45b39f6d5adff9c37d64
Source dataset
uspto-grants-2003_10
Patent number
US06630600B1

Reaction notes

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