Potassium Carbonate → 5-(1-methyl-1H-pyrazol-5-yl)-3-thiophenecarboxylic acid

HRID 1967103Notes

Reaction equation

HRID 1967103 reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]([OH:9])=[O:8])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:16][N:17]1[C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:19]=[N:18]1.CC1(C)COB(C2N(C)N=CC=2)OC1>O1CCOCC1.O.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>[CH3:16][N:17]1[C:21]([C:2]2[S:6][CH:5]=[C:4]([C:7]([OH:9])=[O:8])[CH:3]=2)=[CH:20][CH:19]=[N:18]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 120399785-Bromothiophene-3-carboxylic acidHCID 441194445-(5,5-Dimethyl-1,3,2-dioxaborinan-2-YL)-1-methyl-1H-pyrazole

Product 1

HCID 581103265-(1-methyl-1H-pyrazol-5-yl)-3-thiophenecarboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-3-thiophenecarboxylic acid (875 mg, 4.23 mmol) in dioxane/H2O (5:1, 21 mL) was added K2CO3 (205 mg, 14.8 mmol), tetrakistriphenylphosphine Pd(0) (297 mg, 0.26 mmol) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (988 mg, 4.75 mmol). The reaction mixture was heated to 80° C. in a sealed tube. After 5 h, additional tetrakistriphenylphosphine Pd(0) (108 mg, 0.1 mmol) and 5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1-methyl-1H-pyrazole (989 mg, 4.75 mmol) were added. After 12 h, the reaction solution was then partitioned between H2O—CHCl3, and the aqueous phase was washed several times with CHCl3. The aqueous phase was then adjusted to pH 3 with 2.5M HCl and the aqueous phase extracted with CHCl3. The combined organics were dried (Na2SO4), concentrated under vacuum and dried under high vacuum overnight and used without further purification: LC-MS (ES) m/z=209 (M+H)+.

Workup

  1. waitAfter 12 h
  2. customthe reaction solution was then partitioned between H2O—CHCl3
  3. washthe aqueous phase was washed several times with CHCl3
  4. extractionthe aqueous phase extracted with CHCl3
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. customdried under high vacuum overnight
  8. customused without further purification

Sources & evidence

ORD record
ord-2f6c25f66db5401cbef8ecfb3392bdde
Source dataset
uspto-grants-2013_04
Patent number
US08420690B2

Reaction notes

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