1,4-Difluorobenzene → 1-Benzhydryl-3-(4-fluorophenoxy)azetidine

HRID 341493

反応式

HRID 341493 の反応式
[H-].[Na+].[CH:3]([N:16]1[CH2:19][CH:18]([OH:20])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[H][H].[F:23][C:24]1[CH:29]=[CH:28][C:27](F)=[CH:26][CH:25]=1.C(=O)([O-])O.[Na+]>CN(C=O)C>[C:4]1([CH:3]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:16]2[CH2:19][CH:18]([O:20][C:27]3[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=3)[CH2:17]2)[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

参加物

7

反応物 5

HCID 108921,4-DifluorobenzeneHCID 24758Sodium hydrideHCID 3304481-(Diphenylmethyl)azetidin-3-olHCID 516892Sodium BicarbonateHCID 178418361HCID 178418361、化合物

生成物 1

HCID 150533691-Benzhydryl-3-(4-fluorophenoxy)azetidine収率 67%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a stirred suspension of sodium hydride (60% dispersion in mineral oil, 0.80 g, 20 mmol) in anhydrous DMF (10 ml) under nitrogen was added dropwise a solution of 1-benzhydryl-azetidin-3-ol (3.5 g, 15 mmol) in DMF (10 ml)—Care: hydrogen gas evolution! The mixture was stirred 30 min after gas evolution had ceased then 1,4-difluorobenzene (1.8 mL, 18 mmol) was added dropwise. The mixture was heated to 100 C and stirred for 12 h, then cooled to room temperature and poured into aq sodium hydrogencarbonate solution (50 ml) and extracted twice with EtOAc (2×50 ml). The combined organic layers were washed with water, concentrated under vacuum and purified by flash column chromatography (25 g silica gel; heptane-EtOAc: 1:0-9:1). The product-containing fractions were combined, concentrated under vacuum, washed with heptane and dried under vacuum to give the title compound (3.256 g, 67%). Method B HPLC-MS: MH+ requires m/z=334 Found: m/z=334, Rt=1.69 min (89%). 1H NMR (250 MHz, CDCl3) δ ppm 7.48-7.39 (4H, m), 7.39-7.12 (6H, m), 6.94 (2H, t), 6.71 (2H, dd), 4.75 (1H, m), 4.46 (1H, s), 3.78-3.65 (2H, m), and 3.20-3.07 (2H, m).

後処理

  1. temperatureThe mixture was heated to 100 C
  2. stirringstirred for 12 h
  3. extractionextracted twice with EtOAc (2×50 ml)
  4. washThe combined organic layers were washed with water
  5. concentrationconcentrated under vacuum
  6. custompurified by flash column chromatography (25 g silica gel; heptane-EtOAc: 1:0-9:1)
  7. concentrationconcentrated under vacuum
  8. washwashed with heptane
  9. customdried under vacuum

出典と根拠

ORDレコード
ord-100ed274f3804448b70343ad649a3846
出典データセット
uspto-grants-2014_11
特許番号
US08895733B2

関連ノート

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