Hydrochloric Acid → 1-(4-Fluorophenyl)-4-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)butan-1-one hydrochloride

HRID 10205

반응식

HRID 10205 반응식
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH2:12][CH:13]2[CH2:16][NH:15][CH2:14]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[Cl:25][CH2:26][CH2:27][CH2:28][C:29]([C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1)=[O:30].Cl>CCOC(C)=O.C(OCC)C.CC(=O)CC>[ClH:25].[F:37][C:34]1[CH:33]=[CH:32][C:31]([C:29](=[O:30])[CH2:28][CH2:27][CH2:26][N:15]2[CH2:16][CH:13]([CH2:12][S:9]([C:6]3[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=3)(=[O:11])=[O:10])[CH2:14]2)=[CH:36][CH:35]=1

참가 물질

9

반응물 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 197503-(4-Fluorobenzoyl)propyl chlorideHCID 219783933-{[(4-Fluorophenyl)sulfonyl]methyl}azetidine hydrochloride

생성물 1

HCID 116763311-(4-Fluorophenyl)-4-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)butan-1-one hydrochloride수율 6.6%

시약·촉매·용매 3

HCID 3283Diethyl Ether용매HCID 6569Methyl Ethyl Ketone용매HCID 8857Ethyl Acetate용매

실험 절차

A stirred mixture of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (150 mg, 0.56 mmol), 2-butanone (5 mL), potassium carbonate (0.25 g, 1.81 mmol), sodium iodide (20 mg, 0.13 mmol) and 4-chloro-1-(4-fluorophenyl)butan-1-one (115 μL, 0.68 mmol) was heated at reflux for 5 h under an inert atmosphere. The cooled reaction mixture was partitioned between EtOAc and water. The EtOAc extracts were washed with water and saturated brine then dried (MgSO4), filtered and concentrated in vacuo. The resultant material was purified by column chromatography on silica eluted with a gradient of 0–15% MeOH-EtOAc to give the free base. This was dissolved in EtOAc and treated with 1M HCl in diethyl ether. The solvents was removed in vacuo to give 1-(4-fluorophenyl)-4-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)butan-1-one hydrochloride as a white solid (16 mg). 1H NMR (400 MHz, CD3OD) δ 1.90–1.99 (2H, m), 3.17 (2H, t, J=6.6 Hz), 3.25–3.35 (3H, m), 3.68 (2H, d, J=7.3 Hz), 4.0–4.2 (2H, br s), 4.2–4.4 (2H, br s), 7.20–7.27 (2H, m), 7.39–7.46 (2H, m), 7.98–8.04 (2H, m), 8.05–8.10 (2H, m). m/z (ES+) 394 (M+H)+.

후처리

  1. temperaturewas heated
  2. temperatureat reflux for 5 h under an inert atmosphere
  3. customThe cooled reaction mixture
  4. customwas partitioned between EtOAc and water
  5. washThe EtOAc extracts were washed with water and saturated brine
  6. dry with materialthen dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resultant material was purified by column chromatography on silica
  10. washeluted with a gradient of 0–15% MeOH-EtOAc
  11. customto give the free base
  12. customThe solvents was removed in vacuo

출처 및 근거

ORD 기록
ord-1c558c163b0846259c1e384d3e1982e0
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094777B2

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