Sodium Carbonate → 2-(2-Fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid

HRID 1990993Notes

Reaction equation

HRID 1990993 reaction equation
C([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[S:9][CH:10]=1)=[O:5])C.CO[C:14]1(B(O)O)[C:19]([F:20])=[CH:18][CH:17]=[CH:16][CH2:15]1.[C:24](=[O:27])([O-])[O-].[Na+].[Na+]>COCCOC.CN(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>[F:20][C:19]1[CH:14]=[CH:15][CH:16]=[C:17]([O:27][CH3:24])[C:18]=1[C:8]1[S:9][CH:10]=[C:6]([C:4]([OH:3])=[O:5])[N:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 353965Ethyl 2-bromo-1,3-thiazole-4-carboxylateHCID 866136741-Methoxy-6-flurophenylboronic acid

Product 1

HCID 589248452-(2-Fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Tetrakis(triphenylphosphine)palladium (0.54 g, 0.48 mmol, 2.2% mol eq) was added to a degassed (nitrogen) mixture of 2-bromo-thiazole-4-carboxylic acid ethyl ester (Combi-Blocks, Inc., San Diego, Calif.; 5 g, 21.2 mmol), 1-methoxy-6-flurophenylboronic acid (4.68 g, 27.56 mmol), and sodium carbonate(23 mL, 2 M solution in water) in DME (100 mL) and DMF (100 mL). The reaction mixture was refluxed under inert atmosphere overnight. After cooling to room temperature, the reaction mixture was filtered through celite, and water and EtOAc were added. The aqueous layer was separated, acidified with conc. HCl to pH 2 and then was extracted three times with EtOAc. The combined EtOAc layers were dried under vacuum. The residue was chromatographed on silica, eluting with EtOAc/Hexane (0-30% gradient) to give 2-(2-fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid (4.5 g) which was used directly in the next step.

Workup

  1. customa degassed
  2. temperatureThe reaction mixture was refluxed under inert atmosphere overnight
  3. filtrationthe reaction mixture was filtered through celite, and water and EtOAc
  4. additionwere added
  5. customThe aqueous layer was separated
  6. extractionwas extracted three times with EtOAc
  7. dry with materialThe combined EtOAc layers were dried under vacuum
  8. customThe residue was chromatographed on silica
  9. washeluting with EtOAc/Hexane (0-30% gradient)

Sources & evidence

ORD record
ord-08e6939888104eaba9be008a42dc1356
Source dataset
uspto-grants-2010_01
Patent number
US07645773B2

Reaction notes

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