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

HRID 43012

Reaktionsgleichung

Reaktionsgleichung von HRID 43012
O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C@H:7]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6]2.S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[F:33][C:34]([F:46])([F:45])[C:35]1[C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:38][NH:37][N:36]=1>C(Cl)Cl.CN(C=O)C>[CH2:15]([O:14][C:13]([NH:12][C@@H:7]1[CH2:6][C:5]2[C:9](=[CH:10][CH:11]=[C:3]([CH2:2][N:36]3[C:35]([C:34]([F:46])([F:33])[F:45])=[C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH:38]=[N:37]3)[CH:4]=2)[CH2:8]1)=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 70224068(S)-benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamateHCID 178469923HCID 178469923, Verbindung

Produkt 1

HCID 70244523(S)-Ethyl 1-((2-(benzyloxycarbonylamino)-2,3-dihydro-1H-inden-5-yl)methyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylateAusbeute 3,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(S)-Benzyl 5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate (2.96 mmol, 880 mg) was dissolved in DCM (10 mL) and thionyl chloride (5.92 mmol, 0.432 ml, 704 mg) added. The mixture was stirred at room temperature for 30 min TLC before the solvent was removed under reduced pressure and residual thionylchloride azeotroped with DCM (×3). To the residue was added potassium carbonate (8.88 mmol, 1227 mg) followed by DMF (8 ml) then ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.96 mmol, 616 mg) and the mixture heated to 60° C. After 1 h the mixture was concentrated and partitioned between EtOAc/H2O and the organic layer was washed with water (×3). The organic layer was dried, filtered and concentrated to give a yellow oil which was purified by flash chromatography eluting with 15% EtOAc/Heptane to give the desired isomer as a colourless oil (45 mg, 0.092 mmol, 3.1%). 1H NMR (400 MHz, CDCl3) δ 1.34 (t, 3H) 2.75 (m, 2H) 3.25 (m, 2H) 4.33 (q, 2H), 4.50 (m, 1H) 4.95 (m, 1H), 5.08 (s, 2H) 5.48 (s, 2H) 7.00 (m, 2H) 7.15 (d, 1H) 7.34 (m, 5H) 7.99 (s, 1H).

Aufarbeitung

  1. customwas removed under reduced pressure and residual thionylchloride
  2. customazeotroped with DCM (×3)
  3. concentrationAfter 1 h the mixture was concentrated
  4. custompartitioned between EtOAc/H2O
  5. washthe organic layer was washed with water (×3)
  6. customThe organic layer was dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow oil which
  10. customwas purified by flash chromatography
  11. washeluting with 15% EtOAc/Heptane

Quellen und Nachweise

ORD-Eintrag
ord-1f8ee166ea494577aee895538f08d7c0
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536214B2

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