Hydrochloric Acid → (4'-{1-ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)-acetic Acid

HRID 547063Notes

Reaction equation

HRID 547063 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:41])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([CH2:37][CH3:38])([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]([OH:35])[C:31]([CH3:34])([CH3:33])[CH3:32])=[C:24]([CH3:36])[CH:23]=3)[CH2:20][CH3:21])=[CH:15][C:14]=2[CH3:39])=[CH:9][C:8]=1[F:40].Cl>CO>[CH2:20]([C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:10]2[CH:11]=[CH:12][C:7]([CH2:6][C:5]([OH:41])=[O:4])=[C:8]([F:40])[CH:9]=2)=[C:14]([CH3:39])[CH:15]=1)([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]([OH:35])[C:31]([CH3:33])([CH3:34])[CH3:32])=[C:24]([CH3:36])[CH:23]=1)[CH2:37][CH3:38])[CH3:21]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 57708937(4'-{1-Ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)acetic acid methyl ester

Product 1

HCID 15942405(4'-{1-ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)-acetic AcidYield 103.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A 2 N sodium hydroxide aqueous solution (0.20 mL) was added to a solution of optically active (4′-{1-ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-3-fluoro-2′-methyl-biphenyl-4-yl)-acetic acid methyl ester (Example 141-(1); 33.0 mg, 38%, >99.8% e.e.) in methanol (1.0 mL), and the mixture was stirred with microwave heating at 100° C. for five minutes. A 2 N hydrochloric acid aqueous solution (0.30 mL) was added to the reaction mixture, followed by extraction with ethyl acetate and washing with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (dichloromethane:methanol=100:0 to 90:10) to give the target compound as a colorless oil (33.2 mg, 100%).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washwashing with brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel chromatography (dichloromethane:methanol=100:0 to 90:10)

Sources & evidence

ORD record
ord-58547cdf2bda46209c9a82313a975150
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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