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

HRID 416925Notes

Reaction equation

HRID 416925 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 11673339ChlorotitaniumtriisopropoxideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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+)].

Workup

  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

Sources & evidence

ORD record
ord-2ee6af89e6fd4021816d016ba1a1c32d
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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