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

HRID 1845452Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1845452
Br[C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[CH3:7].C(=O)([O-])[O-].[K+].[K+].[CH3:18][N:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][CH:21]=[N:20]1>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>[CH3:7][C:6]1[S:5][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]=1[C:23]1[N:19]([CH3:18])[N:20]=[CH:21][CH:22]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18536848Methyl 4-bromo-5-methylthiophene-2-carboxylate

Produkt 1

HCID 57826485methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418851HCID 178418851, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of methyl 4-bromo-5-methyl-2-thiophenecarboxylate (2 g, 8.51 mmol) [prepared in Preparation 10], potassium carbonate (5.88 g, 42.5 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.124 g, 10.21 mmol) [prepared according to Preparation 7] and bis(tri-t-butylphosphine)palladium(0) (0.217 g, 0.425 mmol) in 1,4-Dioxane (35.4 ml) and H2O (7.09 ml) was stirred at 80° C. in a sealed tube for 1 h. The reaction mixture was then partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 25% EtOAc in hexanes) affording methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate. This reaction was run in several batches (1 g, 3×2 g) which were combined for workup and purification affording the title compound (5.5 g, 78% combined yield) as a viscous yellow oil: LCMS (ES) m/e 236 (M+H)+.

Aufarbeitung

  1. customThe reaction mixture was then partitioned between H2O-DCM
  2. washthe aqueous phase was washed several times with DCM
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. concentrationconcentrated
  5. custompurified via column chromatography (silica, 25% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-e1981bdc12c649a4a0e9cd513f4623ab
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946278B2

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