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

HRID 10206

반응식

HRID 10206 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

HCID 116689282-(3-{[(2,4-Difluorophenyl)sulfonyl]methyl}azetidin-1-yl)-1-(4-fluorophenyl)ethanone hydrochloride수율 13.6%

시약·촉매·용매 4

HCID 962Water용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-31271072559247c18d69d3585f821af2
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094777B2

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