Hydrochloric Acid → 2-(3-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidin-1-yl)-1-(4-fluorophenyl)ethanone hydrochloride

HRID 10206

Reaktionsgleichung

Reaktionsgleichung von HRID 10206
[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[S:10]([CH2:13][CH:14]1[CH2:17][NH:16][CH2:15]1)(=[O:12])=[O:11].Br[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)=[O:21].C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.CCOC(C)=O.C(OCC)C.O>[ClH:1].[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[S:10]([CH2:13][CH:14]1[CH2:15][N:16]([CH2:19][C:20]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[O:21])[CH2:17]1)(=[O:12])=[O:11]

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 967492-Bromo-1-(4-fluorophenyl)ethan-1-oneHCID 219783663-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidine hydrochloride

Produkt 1

HCID 116689282-(3-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidin-1-yl)-1-(4-fluorophenyl)ethanone hydrochlorideAusbeute 13,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

3-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidine hydrochloride (60 mg, 0.21 mmol) and 2-bromo-1-(4-fluorophenyl)ethanone (52 mg, 0.23 mmol) were stirred together at room temperature with K2CO3 (90 mg, 0.65 mmol) in DMF (3 mL) under an inert atmosphere. Water was added to the mixture after 5.5 h and the mixture was then extracted with EtOAc. The organic extracts were washed with water and saturated brine then dried (MgSO4), filtered and concentrated in vacuo. The resultant material was purified using preparative thin layer chromatography on silica eluted with 50% EtOAc-isohexane to give the free base. This was then dissolved in EtOAc and treated with 1M HCl in diethyl ether. The solids was filtered off and dried in vacuo to give 2-(3-{[(2,4-difluorophenyl)sulfonyl]methyl}azetidin-1-yl)-1-(4-fluorophenyl)ethanone hydrochloride as a colourless solid (12 mg). 1H NMR (500 MHz, d6-DMSO) δ 3.09–3.19 (2H, m), 3.95 (2H, d, J=7.1 Hz), 4.01–4.16 (2H, br s), 4.17–4.29 (2H, m), 5.06 (2H, s), 7.40–7.47 (3H, m), 7.70–7.75 (1H, m), 7.91–7.94 (1H, m), 7.99–8.02 (2H, m), 10.72 (1H, br s). m/z (ES+) 384 (M+H)+.

Aufarbeitung

  1. extractionthe mixture was then extracted with EtOAc
  2. washThe organic extracts were washed with water and saturated brine
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant material was purified
  7. washeluted with 50% EtOAc-isohexane
  8. customto give the free base
  9. filtrationThe solids was filtered off
  10. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-31271072559247c18d69d3585f821af2
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07094777B2

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