Cesium carbonate → 1-{3-[5-Bromo-2-(5-trifluoromethyl-furan-2-ylmethoxy)-benzyl]-azetidin-1-yl}-2,2,2-trifluoro-ethanone

HRID 237302Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 237302
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:19])=[C:6]([CH:18]=1)[CH2:7][CH:8]1[CH2:11][N:10]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:9]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:27][C:28]1[O:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:27][C:28]2[O:29][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:31][CH:32]=2)=[C:6]([CH:18]=1)[CH2:7][CH:8]1[CH2:11][N:10]([C:12](=[O:17])[C:13]([F:15])([F:16])[F:14])[CH2:9]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 584051121-[3-(5-Bromo-2-hydroxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone

Produkt 1

HCID 866570631-{3-[5-Bromo-2-(5-trifluoromethyl-furan-2-ylmethoxy)-benzyl]-azetidin-1-yl}-2,2,2-trifluoro-ethanoneAusbeute 91,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 1-[3-(5-bromo-2-hydroxy-benzyl)-azetidin-1-yl]-2,2,2-trifluoro-ethanone (59 mg, 0.17 mmol) in DMF (10 mL) was added KI (40 mg, 0.24 mmol), Cs2CO3 (170 mg, 0.51 mmol) and 2-bromomethyl-5-trifluoromethyl-furan (56 mg, 0.24 mmol). After 16 h, saturated sodium bicarbonate solution and EtOAc were added. The aqueous portion was extracted three times with EtOAc and the combined organic were dried (Na2SO4) and concentrated. The crude product was purified by RP HPLC (basic conditions) to provide the title compound (76 mg, 91%). MS (ESI): mass calcd. for C18H14BrF6NO3, 486.2; m/z found, 488.1 [M+H]+. 1H NMR (CDCl3): 7.34 (dd, J=8.7, 2.5 Hz, 1H), 7.21 (d, J=2.5 Hz, 1H), 6.89-6.76 (m, 2H), 6.48 (d, J=3.4 Hz, 1H), 5.02 (s, 2H), 4.40 (dd, J=9.6, 8.4 Hz, 1H), 4.22-4.11 (m, 1H), 4.08-4.02 (m, 1H), 3.84 (dd, J=10.7, 5.7 Hz, 1H), 3.11-2.97 (m, 1H), 2.97-2.82 (m, 2H).

Aufarbeitung

  1. extractionThe aqueous portion was extracted three times with EtOAc
  2. dry with materialthe combined organic were dried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by RP HPLC (basic conditions)

Quellen und Nachweise

ORD-Eintrag
ord-ed2f275d40e14e7789927e4cf81f462d
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08642583B2

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