Ammonia → tert-Butyl 4-((1-methyl-1H-imidazol-4-yl)methyl)piperazine-1-carboxylate

HRID 416925노트

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HRID 416925 반응식
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:14][N:15]1[CH:19]=[C:18]([CH:20]=O)[N:17]=[CH:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].N>C(Cl)Cl.CCOC(C)=O.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3]>[CH3:14][N:15]1[CH:19]=[C:18]([CH2:20][N:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]2)[N:17]=[CH:16]1

참가 물질

8

반응물 4

HCID 222AmmoniaHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5734191-Methyl-1H-imidazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydride

생성물 1

HCID 57897298tert-Butyl 4-((1-methyl-1H-imidazol-4-yl)methyl)piperazine-1-carboxylate수율 62%

시약·촉매·용매 3

HCID 11673339Chlorotitaniumtriisopropoxide촉매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

N-Boc-piperazine (0.470 g, 2.50 mmol, 1.1 eq) was dissolved in DCM (6.2 mL). To this solution, 1-methyl-1H-imidazole-4-carboxaldehyde (0.250 g, 2.27 mmol, 1 eq) was added followed by chlorotitanium triisopropoxide (1.19 mL, 5.0 mmol, 2.2 eq). The resulting solution was stirred at room temperature for 10 min before the addition of sodium triacetoxyborohydride (2.40 g, 11.3 mmol, 5 eq). The mixture was stirred at room temperature for 17 h and was diluted with EtOAc (12 mL). It was then poured into ammonia (35% sol. in H2O, 6 mL) and the resulting mixture filtered and washed with EtOAc. The organic phase was washed with H2O dried (MgSO4) and the solvent removed in vacuo. The crude material was purified by column chromatography on a Biotage SP1 system eluting with methanol (1-8%) in dichloromethane to give the title compound as a clear oil (0.390 g, 62%); 1H-NMR (500 MHz, CDCl3): δ 1.46 (s, 9H, C(CH3)3), 2.48 (t, J=5.0 Hz, 4H, piperazine N(CH2)2), 3.45 (t, J=5.0 Hz, 4H, piperazine N(CH2)2), 3.52 (s, 2H, NCH2), 3.66 (s, 3H, imidazole Me), 6.80 (s, 1H, imidazole 5-H), 7.38 (s, 1H, imidazole 2-H); LC (Method B)-MS (ESI, m/z): 281 [(M+H+)].

후처리

  1. filtrationthe resulting mixture filtered
  2. washwashed with EtOAc
  3. washThe organic phase was washed with H2O
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed in vacuo
  6. customThe crude material was purified by column chromatography on a Biotage SP1 system
  7. washeluting with methanol (1-8%) in dichloromethane

출처 및 근거

ORD 기록
ord-2ee6af89e6fd4021816d016ba1a1c32d
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088761B2

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