Ethanol → HCID 18319926, compound

HRID 1699468Notes

Reaction equation

HRID 1699468 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])[CH3:3].[F:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[CH:27]=[CH:26][N:25]=[C:24]2[NH2:28])=[CH:18][CH:17]=1.C(O)C.[BH4-].[Na+]>O>[F:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:22][N:23]2[CH:27]=[CH:26][N:25]=[C:24]2[NH:28][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH2:9][CH2:10]2)=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 4311764Sodium borohydrideHCID 183199421H-Imidazol-2-amine, 1-[(4-fluorophenyl)methyl]-

Product 1

HCID 18319926HCID 18319926, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-Oxo-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (0.053 mol), 1-[(4-fluorophenyl)methyl]-1H-imidazol-2-amine and titanium(IV)isopropoxyde (0.055 mol) were stirred at 50° C. for 2 hours. Ethanol (350 ml) and sodium borohydride (0.53 mol) were added. The mixture was stirred at RT overnight and water was added. The mixture was filtered over decalite, washed with ethanol/CH2Cl2 and the solvent was evaporated. The residue was taken up in CH2Cl2, dried, filtered and the solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2Cl2/CH3OH 100/0, 99/1, 98/2, 97/3, 96/4 and 94/6). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from DIPE and the precipitate was filtered off and dried, yielding 11.3 g (57%) of 1,1-dimethylethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-imidazol-2-yl]amino]-1-piperidinecarboxylate (intermediate 29).

Workup

  1. filtrationThe mixture was filtered over decalite
  2. washwashed with ethanol/CH2Cl2
  3. customthe solvent was evaporated
  4. customdried
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe residue was purified over silica gel on a glass
  8. filtrationfilter (eluent: CH2Cl2/CH3OH 100/0, 99/1, 98/2, 97/3, 96/4 and 94/6)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. customThe residue was crystallized from DIPE
  12. filtrationthe precipitate was filtered off
  13. customdried

Sources & evidence

ORD record
ord-68c77b1dd5544c24830cf34a306ac445
Source dataset
uspto-grants-2002_02
Patent number
US06346540B1

Reaction notes

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