Potassium Carbonate → methyl 5-chloro-4-(1,4-dimethyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

HRID 2392217Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[Cl:7].[CH3:12][N:13]1[C:17](B2OC(C)(C)C(C)(C)O2)=[C:16]([CH3:27])[CH:15]=[N:14]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:7][C:6]1[S:5][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]=1[C:17]1[N:13]([CH3:12])[N:14]=[CH:15][C:16]=1[CH3:27]

Participants

Conditions

Temperature: 85 °C

Procedure

To a 350 mL sealed flask reactor was added methyl 4-bromo-5-chloro-2-thiophenecarboxylate (409 mg, 1.60 mmol) [prepared according to the procedure of Example 95], 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (388 mg, 1.75 mmol) [prepared according to the procedure of Preparation 17], K2CO3 (676 mg, 4.89 mmol) and Pd(PtBu3)2 (32 mg, 0.06 mmol) in 1,4-Dioxane (6 mL) and water (1.5 mL). The reaction was heated at 85° C. for 3 hours. The reaction was partitioned between CHCl3/H2O and the pH of the aqueous layer was adjusted to ˜3 with 6N HCl. The separated organic layer was dried with Na2SO4, adsorbed onto silica and purified via column chromatography (10-65% EtOAc/Hexanes) affording the title compound (106 mg, 0.39 mmol, %); LC-MS (ES) m/z=271 (M+H)+.

Workup

customTo a 350 mL sealed flask reactor
customprepared
customprepared
customThe reaction was partitioned between CHCl3/H2O
dry with materialThe separated organic layer was dried with Na2SO4
custompurified via column chromatography (10-65% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-4fff69e33b874abc9bf9735b6fe9147b
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273782B2

Reaction notes

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