Hydrochloric Acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-one

HRID 28522

反応式

HRID 28522 の反応式
Cl.CO[CH:4]1[CH2:8][CH2:7][CH:6](OC)[O:5]1.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH2:19]([C:26](O)=O)[C:20](CC(O)=O)=O.P([O-])([O-])(O)=O.[Na+].[Na+].[OH-].[Na+]>O>[CH2:11]([N:18]1[CH:7]2[CH2:6][CH2:26][CH:19]1[CH2:20][C:4](=[O:5])[CH2:8]2)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

参加物

8

反応物 6

HCID 313Hydrochloric Acid3 回HCID 7504Benzylamine2 回HCID 14798Sodium Hydroxide2 回HCID 24203Sodium Phosphate, DibasicHCID 68328Acetonedicarboxylic acidHCID 790982,5-Dimethoxytetrahydrofuran2 回

生成物 1

HCID 1198468-Benzyl-8-azabicyclo(3.2.1)octan-3-one

試薬・触媒・溶媒 1

HCID 962Water溶媒5 回

反応条件

温度
85 °C

実験手順

Concentrated hydrochloric acid (30 mL) was added to a heterogeneous solution of 2,5-dimethoxy tetrahydrofuran (82.2 g, 0.622 mol) in water (170 mL) while stirring. In a separate flask cooled to 0° C. (ice bath), concentrated hydrochloric acid (92 mL) was added slowly to a solution of benzyl amine (100 g, 0.933 mol) in water (350 mL). The 2,5-dimethoxytetrahydrofuran solution was stirred for approximately 20 min, diluted with water (250 mL), and then the benzyl amine solution was added, followed by the addition of a solution of 1,3-acetonedicarboxylic acid (100 g, 0.684 mol) in water (400 mL) and then the addition of sodium hydrogen phosphate (44 g, 0.31 mol) in water (200 mL). The pH was adjusted from pH 1 to pH˜4.5 using 40% NaOH. The resulting cloudy and pale yellow solution was stirred overnight. The solution was then acidified to pH 3 from pH 7.5 using 50% hydrochloric acid, heated to 85° C. and stirred for 2 hours. The solution was cooled to room temperature, basified to pH 12 using 40% NaOH, and extracted with DCM (3×500 mL). The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to afford the title intermediate in quantitative yield as a viscous brown oil (˜95% purity based on analytical HPLC). 1H-NMR (CDCl3) δ (ppm) 7.5-7.2 (m, 5H, C6H5), 3.7 (s, 2H, CH2Ph), 3.45 (broad s, 2H, CH-NBn), 2.7-2.6 (dd, 2H, CH2CO), 2.2-2.1 (dd, 2H, CH2CO), 2.1-2.0 (m, 2H, CH2CH2), 1.6 (mn, 2H, CH2CH2). (m/z): [M+H]+ calcd for C14H17NO 216.14; found, 216.0.

後処理

  1. stirringThe resulting cloudy and pale yellow solution was stirred overnight
  2. stirringstirred for 2 hours
  3. temperatureThe solution was cooled to room temperature
  4. extractionextracted with DCM (3×500 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-4e1b8c18ef2f4d3daf1a3cb0c4d8b926
出典データセット
uspto-grants-2008_09
特許番号
US07419989B2

関連ノート

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