Hydrochloric Acid → 2-(6-Methoxy-3-pyridinyl)-1,3-thiazole-4-carboxylic acid

HRID 460183Notes

Reaction equation

HRID 460183 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([C:13]([O:15]CC)=[O:14])[N:12]=2)=[CH:4][CH:3]=1.C[O-].[Na+].ClC1N=CC(C2([C:33](O)=[O:34])NC=CS2)=CC=1.Cl>CO>[CH3:33][O:34][C:2]1[N:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([C:13]([OH:15])=[O:14])[N:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10942334Sodium Methoxide3×HCID 18771729Ethyl 2-(6-Chloropyridin-3-yl)thiazole-4-carboxylateHCID 878223932-(6-Chloro-3-pyridyl)thiazole carboxylic acid

Product 1

HCID 187717522-(6-Methoxy-3-pyridinyl)-1,3-thiazole-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the ethyl 2-(6-chloro-3-pyridyl)thiazole-4-carboxylate (0.61 g, 2.3 mmol) and MeOH (50 mL) was added solid NaOMe (135 mg, 2.5 mmol) and stirred at RT. After 3 h the ethyl ester transesterified to the methyl ester. NaOMe (1 eq, 135 mg) was added and the mixture was heated to reflux. After 15 h, the ester hydrolyzed to the 2-(6-chloro-3-pyridyl)thiazole carboxylic acid. NaOMe (2 eq) was added and the reaction was heated at reflux for 18 h. The mixture was acidified to pH 5 with concentrated HCl, extracted with EtOAc, washed with H2O and brine; dried (MgSO4) and concentrated in vacuo to give the desired carboxylic acid as a yellow solid. MS m/z: 237.1 (M+H).

Workup

  1. temperaturethe mixture was heated to reflux
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 18 h
  4. extractionextracted with EtOAc
  5. washwashed with H2O and brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a91df795b2e04b03963a548ae9af29d9
Source dataset
uspto-grants-2007_03
Patent number
US07196104B2

Reaction notes

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