Hydrochloric Acid → (E)-3-(4-((E)-1-(1H-Indazol-5-yl)-2-phenylbut-1-en-1-yl)phenyl)acrylic acid

HRID 1254458Notes

Reaction equation

HRID 1254458 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6](/[C:10](/[C:20]3[CH:25]=[CH:24][C:23](/[CH:26]=[CH:27]/[C:28]([O:30]CC)=[O:29])=[CH:22][CH:21]=3)=[C:11](/[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)\[CH2:12][CH3:13])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[Li+].[OH-].Cl>C1COCC1.CCO.O>[NH:1]1[C:9]2[C:4](=[CH:5][C:6](/[C:10](/[C:20]3[CH:21]=[CH:22][C:23](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[CH:24][CH:25]=3)=[C:11](/[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)\[CH2:12][CH3:13])=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66794771(E)-Ethyl 3-(4-((E)-1-(1H-indazol-5-yl)-2-phenylbut-1-en-1-yl)phenyl)acrylate2×

Product 1

HCID 56927060(E)-3-(4-((E)-1-(1H-Indazol-5-yl)-2-phenylbut-1-en-1-yl)phenyl)acrylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

To a solution of (E)-ethyl 3-(4-((E)-1-(1H-indazol-5-yl)-2-phenylbut-1-en-1-yl)phenyl)acrylate (2.5 g, 5.9 mmol; Compound 1) in THF-EtOH (1:1, 59 mL), an aqueous solution of LiOH (2.8 g, 118 mmol; dissolved in a minimum amount of water) was added at room temperature. The resulting mixture was stirred overnight. The reaction was monitored by LCMS. Upon completion, 1N aqueous HCl was added until pH was 3. Then, the mixture was diluted with water and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with water, washed with brine, dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a silica gel column eluted with 0˜20% methanol in dichloromethane affording the title compound as a pale yellow solid (1.9 g). 1H NMR (300 MHz, DMSO-d6): δ 13.11 (s, 1H), 12.30 (br, 1H), 8.08 (s, 1H), 7.65 (s, 1H), 7.53 (d, 1H), 7.43 (d, 1H), 7.37 (d, 2H), 7.29-7.11 (m, 6H), 6.88 (d, 2H), 6.37 (d, 1H), 2.44 (q, 2H), 0.87 (t, 3H); LCMS: 395 (M+H)+.

Workup

  1. additionwas added at room temperature
  2. extractionextracted with ethyl acetate (3×200 mL)
  3. washThe combined organic layers were washed with water
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cc794c344131486eb4c306f005028c7d
Source dataset
uspto-grants-2013_06
Patent number
US08455534B2

Reaction notes

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