Sodium Hydroxide → tert-butyl 4-((5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)methyl)-1-piperidinecarboxylate

HRID 1162327Notes

Reaction equation

HRID 1162327 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[CH3:16][C:17]1[NH:18][CH:19]=[C:20]([CH:22]=O)[N:21]=1.[C:24](O[BH-](OC(=O)C)OC(=O)C)(=[O:26])C.[Na+].[OH-].[Na+]>ClCCCl.C(O)(=O)C>[CH3:16][C:17]1[N:21]2[C:24](=[O:26])[N:1]([CH2:2][CH:3]3[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]3)[CH2:22][C:20]2=[CH:19][N:18]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 178418999HCID 178418999, compound

Product 1

HCID 23138425tert-butyl 4-((5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)methyl)-1-piperidinecarboxylateYield 60.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolvent

Procedure

To a solution of tert-butyl 4-(aminomethyl)-1-piperidinecarboxylate (K. Ito et al., Eur. J. Med. Chem., 34, 977 (1999); 3.7 g), 2-methylimidazole-4-carbaldehyde (1.9 g) and acetic acid (1 ml) in 1,2-dichloroethane (100 ml) was added sodium triacetoxyborohydride (5.6 g), and mixed at room temperature for 15 hours. pH of the aqueous layer was adjusted to about 12 by adding a 1 N aqueous sodium hydroxide solution to the reaction solution, and then extracted with chloroform. The extract was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resulting yellow oil was dissolved in dichloromethane (100 ml), DBU (2.6 ml) and N,N′-carbonyldiimidazole (2.8 g) were added thereto, and mixed at room temperature for 15 hours. The reaction mixture was diluted with water and chloroform and the organic layer was collected by separation, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified with silica gel column (ethyl acetate:ethanol=5:1) to obtain the title compound as a yellow oil (3.5 g, 59%).

Workup

  1. additionmixed at room temperature for 15 hours
  2. extractionextracted with chloroform
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. dissolutionThe resulting yellow oil was dissolved in dichloromethane (100 ml)
  6. additionDBU (2.6 ml) and N,N′-carbonyldiimidazole (2.8 g) were added
  7. additionmixed at room temperature for 15 hours
  8. additionThe reaction mixture was diluted with water and chloroform
  9. customthe organic layer was collected by separation
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationThe solvent was distilled off under reduced pressure
  12. customthe residue was purified with silica gel column (ethyl acetate:ethanol=5:1)

Sources & evidence

ORD record
ord-6fefcfb53ce64118acf453f23acb84d6
Source dataset
uspto-grants-2010_10
Patent number
US07820673B2

Reaction notes

Loading…