Hydrochloric Acid → (E)-3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

HRID 332893Notes

Reaction equation

HRID 332893 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([O:10][C:11]3[CH:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[C:19]([O:21]C)=[O:20])=[CH:13][CH:12]=3)=[C:8]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH:29]([CH3:31])[CH3:30])[S:7][C:6]=2[CH:32]=1.[Li+].[OH-].Cl>CCO>[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([O:10][C:11]3[CH:12]=[CH:13][C:14](/[CH:17]=[CH:18]/[C:19]([OH:21])=[O:20])=[CH:15][CH:16]=3)=[C:8]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH:29]([CH3:30])[CH3:31])[S:7][C:6]=2[CH:32]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86730676(E)-methyl 3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Product 1

HCID 77105904(E)-3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acidYield 96.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Example 4 was be prepared from the corresponding methylether/tert-butyl ester intermediates using method A. Example 4 was also prepared, using the following hydrolysis reaction: to a solution of (E)-methyl 3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (25.8 mg, 0.058 mmol) in EtOH (1.5 mL) was added LiOH (2.0 M aqueous, 0.290 mL, 0.580 mmol). After 5 h at room temperature the reaction was acidified to pH 3 by addition of 1.0 N aqeuous HCl and extracted with 5% MeOH/EtOAc, the combined organic layers were passed through a phase separator and concentrated in vacuo to afford (E)-3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (24.0 mg, 0.056 mmol, 96% yield). LC/MS (m/z, M-H): 429.0.

Workup

  1. customExample 4 was also prepared
  2. customthe following hydrolysis reaction
  3. extractionextracted with 5% MeOH/EtOAc
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9419a06a9a3d46b19d73fe6cdf94c6d5
Source dataset
uspto-grants-2014_11
Patent number
US08877801B2

Reaction notes

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