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Hydrochloric Acid → 5-[2-(Acetylamino)pyridin-4-yl]-3-(4-chlorobenzyl)-4-cyanothiophene-2-carboxylic acid

HRID 2401714
Notes
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Reaction equation

HRID 2401714 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:15][C:14]([C:16]([O:18]CC)=[O:17])=[C:13]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[C:12]=2[C:29]#[N:30])[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2].[OH-].[Li+].Cl>O1CCCC1.O>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:15][C:14]([C:16]([OH:18])=[O:17])=[C:13]([CH2:21][C:22]3[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=3)[C:12]=2[C:29]#[N:30])[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 66747535Ethyl 5-[2-(acetylamino)pyridin-4-yl]-3-(4-chlorobenzyl)-4-cyanothiophene-2-carboxylate

Product 1

HCID 667479655-[2-(Acetylamino)pyridin-4-yl]-3-(4-chlorobenzyl)-4-cyanothiophene-2-carboxylic acidYield 78.2%

Reagents, catalysts & solvents 2

HCID 962
Water
Solvent
HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 5-[2-(acetylamino)pyridin-4-yl]-3-(4-chlorobenzyl)-4-cyanothiophene-2-carboxylate (0.080 g, 0.18 mmol) in tetrahydrofuran (1.28 mL) and water (0.85 mL) was added lithium hydroxide (1.0M solution in water, 0.236 mL, 0.236 mmol). The reaction mixture was stirred at room temperature for 16 hours. The mixture was acidified to pH 6 using aqueous 1N HCl (0.300 mL). The mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, and then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography was performed to yield the title compound (0.058 g, 78%). LCMS: (FA) ES+, 412. 1H NMR (400 MHz, d6-DMSO) δ: 10.72 (s, 1H), 8.46-8.41 (m, 2H), 7.42-7.39 (m, 1H), 7.36-7.32 (m, 4H) 4.53 (s, 2H), 2.11 (s, 3H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-82de178da53c4158816dc3e8dc63fe9b
Source dataset
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08796268B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes