Acetic Acid → Ethyl 4-[4-(ethoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate

HRID 714527ノート

反応式

HRID 714527 の反応式
[NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.[CH2:12]([O:14][C:15]([N:17]1[CH2:23][CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1)=[O:16])[CH3:13].C(O)(=O)C>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH2:8]([O:7][C:5]([CH:4]1[CH2:3][CH2:2][N:1]([CH:20]2[CH2:21][CH2:22][CH2:23][N:17]([C:15]([O:14][CH2:12][CH3:13])=[O:16])[CH2:18][CH2:19]2)[CH2:11][CH2:10]1)=[O:6])[CH3:9]

参加物

6

反応物 3

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 126660861-Carbethoxyazepan-4-one

生成物 1

HCID 89579373Ethyl 4-[4-(ethoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate収率 48.4%

試薬・触媒・溶媒 2

HCID 11026Titanium isopropoxide触媒HCID 6344Dichloromethane溶媒

実験手順

Ethyl isonipecotate (2.54 g, 2.50 mL, 16.2 mmol) and 4-oxoazepane-1-carboxylic acid ethyl ester (3.00 g, 16.2 mmol) were dissolved in DCM (100 mL) at rt and titanium isopropoxide (5.07 g, 5.40 mL, 17.8 mmol) was added. The reaction mixture was stirred at rt for 1 h. STAB (13.7 g, 32.4 mmol) and acetic acid (0.5 mL) were added and the reaction mixture was stirred at rt overnight under nitrogen. The reaction mixture was quenched with the addition of water (5 mL) and stirred for 5 minutes. The reaction mixture was diluted with DCM and filtered through a pad of celite. The filtrate was washed with sat. NaHCO3 sol., sat. NaCl sol. and dried over MgSO4. The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 50 g, 40-63 μm, 60 Å, 50 mL per min, gradient 2% to 4% MeOH in DCM]) to give ethyl 4-[4-(ethoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate (2.56 g, 48%) as a pale yellow oil.

後処理

  1. stirringthe reaction mixture was stirred at rt overnight under nitrogen
  2. customThe reaction mixture was quenched with the addition of water (5 mL)
  3. stirringstirred for 5 minutes
  4. additionThe reaction mixture was diluted with DCM
  5. filtrationfiltered through a pad of celite
  6. washThe filtrate was washed with sat. NaHCO3 sol., sat. NaCl sol.
  7. dry with materialdried over MgSO4
  8. customThe solvents were removed in vacuo
  9. customthe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 50 g, 40-63 μm, 60 Å, 50 mL per min, gradient 2% to 4% MeOH in DCM])

出典と根拠

ORDレコード
ord-a024c909a46345068599e7b5f4da7e91
出典データセット
uspto-grants-2015_11
特許番号
US09187451B2

反応ノート

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