Cesium carbonate → 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic Acid

HRID 1961183Notes

Reaction equation

HRID 1961183 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:7]([OH:9])=[O:8])[S:5][CH:6]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:16][N:17]1[C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:19]=[N:18]1>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[CH:3]=[C:4]([C:7]([OH:9])=[O:8])[S:5][CH:6]=2)=[CH:20][CH:19]=[N:18]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 6104094-Bromo-2-thiophenecarboxylic AcidHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 578264554-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic Acid

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

To a solution of 4-bromo-2-thiophenecarboxylic acid (3.91 g, 18.9 mmol) in dioxane/H2O (4:1, 100 mL) was added Cs2CO3 (21.7 g, 66.6 mmol), tetrakistriphenylphosphine Pd(0) (1.1 g, 0.95 mmol) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.94 g, 18.94 mmol) [prepared according to the procedure of Preparation 7]. The reaction mixture was heated to 85° C. in a sealed tube for 12 hours and partitioned between H2O and CHCl3. The pH of the aqueous phase was adjusted to ˜3 with 6N HCl and washed several times with CHCl3. The combined organic fractions were dried (Na2SO4), concentrated under vacuum and used directly without further purification (2.84 g, 13.64 mmol, 72%): LC-MS (ES) m/z=209 (M+H)+.

Workup

  1. customprepared
  2. customaccording to the procedure of Preparation 7]
  3. custompartitioned between H2O and CHCl3
  4. washwashed several times with CHCl3
  5. dry with materialThe combined organic fractions were dried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. customused directly without further purification (2.84 g, 13.64 mmol, 72%)

Sources & evidence

ORD record
ord-66e8c560d8824862aa1ac824e988a6b3
Source dataset
uspto-grants-2013_04
Patent number
US08410158B2

Reaction notes

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