Water → HCID 22260059, compound

HRID 1270459Notes

Reaction equation

HRID 1270459 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:15]1([C:20]2[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=2)[CH:19]=[CH:18][N:17]=[CH:16]1.[BH3-]C#N.[Na+].O>C(O)C.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[N:15]1([C:20]2[CH:26]=[CH:25][C:23]([NH:24][CH:10]3[CH2:11][CH2:12][CH2:13][N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:9]3)=[CH:22][CH:21]=2)[CH:19]=[CH:18][N:17]=[CH:16]1

Participants

7

Reactant 4

HCID 962WaterHCID 966503-Piperidinone, 1-(phenylmethyl)-HCID 3201654-(1H-imidazol-1-yl)anilineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 22260059HCID 22260059, compoundYield 17.1%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 702EthanolSolvent

Procedure

1-Benzyl-3-piperidinone (2.07 g, 10 mmol), 4-(imidazol-1-yl)aniline (1.73 g, 1.0 eq.), and Ti(OiPr)4 (3.72 mL, 1.25 eq.) were stirred at ambient temperature for 1.25 hours. The mixture was then diluted with absolute ethanol (10 mL) and NaCNBH3 (0.44 g, 0.67 eq.) was added. The resulting mixture was stirred for 20 hours. Water (2 mL) was added to the mixture with stirring and the resulting precipitate was filtered. Flash column chromatography on silical gel with 1–5% methanol in methylene chloride gave a crude product. Further purification by HPLC afforded 3-[(4-(imidazol-1-yl)phenyl)amino]-1-benzylpiperidine (569 mg), which was dissolved in methanol (10 mL) and treated with 10% Pd/C (400 mg) and ammonium formate (800 mg). The resulting mixture was heated at reflux for 4 hours. After cooling to ambient temperature, the mixture was filtered. Evaporation of the solvent in vacuo gave 3-[(4-(imidazol-1-yl)phenyl)amino]piperidine (330 mg, 1.36 mmol).

Workup

  1. additionwas added
  2. stirringwith stirring
  3. filtrationthe resulting precipitate was filtered
  4. customFlash column chromatography on silical gel with 1–5% methanol in methylene chloride gave a crude product
  5. customFurther purification by HPLC

Sources & evidence

ORD record
ord-e75f9157a2644551823413e324275dc2
Source dataset
uspto-grants-2007_04
Patent number
US07202263B2

Reaction notes

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