4-Amino-1-Boc-piperidine → tert-butyl 4-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-ylamino)piperidine-1-carboxylate

HRID 1643491ノート

反応式

HRID 1643491 の反応式
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[F:15][C:16]([F:41])([F:40])[C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][CH:26]([O:29][C:30]3[CH:31]=[C:32]4[C:36](=[CH:37][CH:38]=3)[C:35](=O)[CH2:34][CH2:33]4)[CH2:25][CH2:24]2)=[CH:19][CH:18]=1.[BH4-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[F:41][C:16]([F:15])([F:40])[C:17]1[CH:18]=[CH:19][C:20]([N:23]2[CH2:24][CH2:25][CH:26]([O:29][C:30]3[CH:31]=[C:32]4[C:36](=[CH:37][CH:38]=3)[CH:35]([NH:1][CH:2]3[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]3)[CH2:34][CH2:33]4)[CH2:27][CH2:28]2)=[CH:21][CH:22]=1

参加物

6

反応物 3

HCID 12682914-Amino-1-Boc-piperidineHCID 4311764Sodium borohydrideHCID 667570455-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-one

生成物 1

HCID 57765814tert-butyl 4-(5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-ylamino)piperidine-1-carboxylate収率 65.2%

試薬・触媒・溶媒 2

HCID 11026Titanium isopropoxide触媒HCID 887Methanol溶媒

実験手順

Tert-butyl 4-aminopiperidine-1-carboxylate (0.48 g, 2.4 mmol) and 5-(1-(4-(trifluoromethyl)phenyl)piperidin-4-yloxy)-2,3-dihydro-1H-inden-1-one (0.75 g, 2.0 mmol) were mixed in neat titanium(IV) isopropoxide (2.85 g, 10.0 mmol) and stirred at room temperature overnight. Methanol (10 mL) was added followed by addition of sodium borohydride (0.12 g, 3.2 mmol). The reaction was stirred at room temperature for 3 h and then quenched by adding 0.1N aqueous sodium hydroxide. The resulting mixture was filtered through celite, and the residue was washed with ethyl acetate (2×10 mL) and with dichloromethane (10 mL). The organic layer was separated and dried over sodium sulfate. The drying agent was filtered off, and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, ethyl acetate/hexanes=¼) to afford the title compound as a off-white solid (0.73 g, 65%). 1H NMR (CDCl3, 300 MHz) 7.64 (m, 1H), 7.48 (m, 2H), 6.95 (m, 2H), 6.76 (m, 2H), 4.68 (m, 1H), 4.44 (m, 1H), 3.53 (m, 2H), 3.18 (m, 2H), 2.85 (m, 4H), 2.47 (m, 2H), 2.24-1.79 (m, 12H), 1.46 (s, 9H) ppm; MS (ES) 560.6 (M+H).

後処理

  1. stirringThe reaction was stirred at room temperature for 3 h
  2. customquenched
  3. additionby adding 0.1N aqueous sodium hydroxide
  4. filtrationThe resulting mixture was filtered through celite
  5. washthe residue was washed with ethyl acetate (2×10 mL) and with dichloromethane (10 mL)
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationThe drying agent was filtered off
  9. concentrationthe filtrate concentrated under reduced pressure
  10. customThe residue obtained
  11. customwas purified by flash chromatography (silica gel, ethyl acetate/hexanes=¼)

出典と根拠

ORDレコード
ord-6f65a0ca06d24b159ede806a85743aac
出典データセット
uspto-grants-2012_02
特許番号
US08119809B2

反応ノート

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