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

HRID 10205

反応式

HRID 10205 の反応式
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

参加物

9

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 6569Methyl Ethyl Ketone溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-1c558c163b0846259c1e384d3e1982e0
出典データセット
uspto-grants-2006_08
特許番号
US07094777B2

関連ノート

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