Potassium Carbonate → 4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylic Acid

HRID 1961013Notes

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.[K+].[K+].CC1(C)COB([C:23]2[N:27]([CH3:28])[N:26]=[CH:25][CH:24]=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>[CH3:28][N:27]1[C:23]([C:2]2[CH:3]=[C:4]([C:7]([OH:9])=[O:8])[S:5][CH:6]=2)=[CH:24][CH:25]=[N:26]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-bromo-2-thiophenecarboxylic acid (1 g, 4.83 mmol) in dioxane/H2O (5:1, 16 mL) was added K2CO3 (2.7 g, 19 mmol), tetrakistriphenylphosphine Pd(0) (279 mg, 0.241 mmol) and 5-(5,5-dimethyl-1,3,2-dioxaborinane-2-yl)-1-methyl-1H-pyrazole (1.2 g, 6.27 mmol). The reaction mixture was heated to 80° C. in a sealed tube for 2 h and additional tetrakistriphenylphosphine Pd(0) (279 mg, 0.241 mmol) and 5-(5,5-dimethyl-1,3,2-dioxaborinane-2-yl)-1-methyl-1H-pyrazole (1.2 g, 6.27 mmol) were added. After 12 h, the reaction was partitioned between 6N NaOH and DCM. The pH of the aqueous phase was adjusted to ˜3 with 3M HCl and washed several times with DCM. The combined organic fractions were dried (Na2SO4), concentrated under vacuum and used directly without further purification (˜1 g, quant.): LCMS (ES) m/z=209 (M+H)+.

Workup

customthe reaction was partitioned between 6N NaOH and DCM
washwashed several times with DCM
dry with materialThe combined organic fractions were dried (Na2SO4)
concentrationconcentrated under vacuum
customused directly without further purification (˜1 g, quant.)

Sources & evidence

ORD record: ord-9b14c8ec70764e6d8f8454088c04995f
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410158B2

Reaction notes

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