Sodium Carbonate → 3,5-dimethyl-4-(2-trifluoromethyl-phenyl)-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 383756Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 383756
Br[C:2]1[C:3]([CH3:13])=[C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[NH:5][C:6]=1[CH3:7].[F:14][C:15]([F:26])([F:25])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.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>[CH2:11]([O:10][C:8]([C:4]1[NH:5][C:6]([CH3:7])=[C:2]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]([F:26])([F:25])[F:14])[C:3]=1[CH3:13])=[O:9])[CH3:12]

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 138486ethyl 4-bromo-3,5-dimethyl-1H-pyrrole-2-carboxylateHCID 27343872-(Trifluoromethyl)benzeneboronic acid

Produkt 1

HCID 598075413,5-dimethyl-4-(2-trifluoromethyl-phenyl)-1H-pyrrole-2-carboxylic acid ethyl esterAusbeute 48,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of ethyl 3,5-dimethyl-1H-pyrrole-2-carboxylate (3.42 g, 20 mmol) in carbon tetrachloride (40 mL) was added a solution of bromine in carbon tetrachloride (10 mL) dropwise at 20° C. After the addition was complete, stirring was continued for 2 h. The reaction mixture was diluted with DCM, washed with aqueous NaHCO3 and water, and then dried over Na2SO4. Evaporation of solvent gave ethyl 4-bromo-3,5-dimethyl-1H-pyrrole-2-carboxylate as a solid (4.8 g), which was used in the next step without purification. 1H-NMR (CDCl3): δ 9.36 (1H, s), 4.30 (2H, q), 228 (3H, s), 2.26 (3H, s), 1.36 (3H, t). To a solution of ethyl 4-bromo-3,5-dimethyl-1H-pyrrole-2-carboxylate (2.4 g, 10 mmol) in DMF (25 mL) was added tetrakis(triphenylphosphine)palladium (2.3 g, 1 mmol). After stirring 15 min, the reaction mixture was charged with 2-(trifluoromethyl)-benzeneboronic acid (2.4 g, 12.5 mmol) and sodium carbonate (in 5 mL of water). The reaction mixture was heated to reflux overnight with stirring. After cooling, the reaction mixture was then diluted with water and extracted with DCM. The combined extracts were washed with water and dried over Na2SO4. Evaporation of solvent gave a crude material, which was purified by chromatography on silica gel column eluting with EtOAc-hexane (1:1) to give the title compound (1.5 g). MS (ES): 312 (MH+);

Aufarbeitung

  1. customwas used in the next step without purification
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux overnight
  4. stirringwith stirring
  5. temperatureAfter cooling
  6. extractionextracted with DCM
  7. washThe combined extracts were washed with water
  8. dry with materialdried over Na2SO4
  9. customEvaporation of solvent
  10. customgave a crude material, which
  11. customwas purified by chromatography on silica gel column
  12. washeluting with EtOAc-hexane (1:1)

Quellen und Nachweise

ORD-Eintrag
ord-2d3e61e4b5684631ab160a843e04781f
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367667B2

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