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 1046515노트

반응식

HRID 1046515 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 11026Titanium isopropoxide촉매HCID 887Methanol용매

실험 절차

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=1/4) 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).

후처리

  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=1/4)

출처 및 근거

ORD 기록
ord-86e30264a64c46c28164ee79b900d562
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569340B2

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