Potassium Carbonate → Ethyl 2-(6-chloropyridin-3-yl)-4-methyl-1,3-thiazole-5-carboxylate

HRID 1710787Notes

Reaction equation

HRID 1710787 reaction equation
Br[C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([CH3:7])[N:6]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][N:15]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:13][C:14]1[N:15]=[CH:16][C:17]([C:2]2[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([CH3:7])[N:6]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2824057Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylateHCID 38450342-Chloropyridine-5-boronic acid

Product 1

HCID 59457501Ethyl 2-(6-chloropyridin-3-yl)-4-methyl-1,3-thiazole-5-carboxylateYield 69.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Procedure

Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate (1 g, 1.3 eq, 4 mmol) is added to a mixture of 2-chloro-5-pyridine boronic acid (0.48 g, 1 eq, 3.07 mmol), tetrakis(triphenylphosphine)palladium (0.18 g, 0.05 eq, 0.15 mmol) and an aqueous solution of 2 M potassium carbonate (3 ml, 2 eq, 6.14 mmol) in toluene/ethanol (18 ml, 2:1 v/v). The mixture is refluxed overnight and the solvent is evaporated, then taken up in ethyl acetate, and washed two times with an aqueous solution of sodium hydrogenocarbonate. The organic layer is dried over magnesium sulfate, filtered and concentrated under vacuum. Purification by chromatography over silicagel (eluent: dichloromethane 100%) affords 0.6 g of ethyl 2-(6-chloropyridin-3-yl)-4-methyl-1,3-thiazole-5-carboxylate i97.

Workup

  1. temperatureThe mixture is refluxed overnight
  2. customthe solvent is evaporated
  3. washwashed two times with an aqueous solution of sodium hydrogenocarbonate
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customPurification by chromatography over silicagel (eluent: dichloromethane 100%)

Sources & evidence

ORD record
ord-089c1b3c6cfb495f9c7494c438d9c2fb
Source dataset
uspto-grants-2010_09
Patent number
US07790720B2

Reaction notes

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