Potassium Carbonate → Ethyl 1-((1-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 43018Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 43018
O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH:8]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7][CH2:6]2.S(Cl)(Cl)=O.[F:27][C:28]([F:40])([F:39])[C:29]1[C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:32][NH:31][N:30]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CN(C=O)C.[NH4+].[Cl-].O>[CH2:15]([O:14][C:13]([NH:12][CH:8]1[C:9]2[C:5](=[CH:4][C:3]([CH2:2][N:31]3[CH:32]=[C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:29]([C:28]([F:27])([F:39])[F:40])=[N:30]3)=[CH:11][CH:10]=2)[CH2:6][CH2:7]1)=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Komponenten

9

Edukt 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67088218Benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-1-ylcarbamateHCID 178469923HCID 178469923, Verbindung

Produkt 1

HCID 67088120Ethyl 1-((1-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

To a solution of benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-1-ylcarbamate (6.73 mmol, 2.0 g) in DCM (15 ml) was added thionyl chloride (13.45 mmol, 0.0.98 mL) and the whole was stirred for 2 h at room temperature after which time LCMS suggested 100% conversion to product. The reaction mixture was concentrated under reduced pressure and the residue re-dissolved in DCM. This was repeated a further 4 times to give a light yellow solid. This was dissolved in DMF (25 mL) and ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (1.29 g, 6.17 mmol) was added followed by potassium carbonate (18.52 mmol, 2.56 g). The resulting suspension was heated to 60° C. and this temperature was maintained for 2 h after the reaction mixture was diluted with sat NH4Cl followed by water and the organics extracted with EtOAc (2×100 mL), dried (1PS paper) and concentrated under reduced pressure. The residue was then purified by flash chromatography (40% EtOAc/heptane) to give a white solid (2.54, 5.21 mmol, 84%). 1H NMR (400 MHz, CDCl3) δ 1.34 (t, 3H) 1.85 (m, 1H) 2.12 (m, 1H) 2.85 (m, 1H) 2.95 (m, 1H) 4.28 (q, 2H) 4.95 (d, 1H), 5.16 (s, 1H) 5.25 (m, 1H) 5.29 (s, 2H) 7.13 (brs, 2H) 7.35 (m, 6H), 7.87 (s, 1H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue re-dissolved in DCM
  3. customto give a light yellow solid
  4. temperatureThe resulting suspension was heated to 60° C.
  5. temperaturethis temperature was maintained for 2 h after the reaction mixture
  6. extractionthe organics extracted with EtOAc (2×100 mL)
  7. customdried (1PS paper)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was then purified by flash chromatography (40% EtOAc/heptane)
  10. customto give a white solid (2.54, 5.21 mmol, 84%)

Quellen und Nachweise

ORD-Eintrag
ord-bac286ee6b1a4851ae5e9c4430c81f7a
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536214B2

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