Hydrochloric Acid → N-{[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]methyl}-4-(3-methylphenyl)-4 hydroxy piperidine

HRID 443217Notes

Reaction equation

HRID 443217 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[C:5]([C:9]2([OH:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.[C:16]([C:18]1[CH:31]=[CH:30][C:21]([CH2:22][N:23]2[C:27]([CH:28]=O)=[CH:26][N:25]=[CH:24]2)=[CH:20][CH:19]=1)#[N:17].C([BH3-])#N.[Na+].Cl>CO.C1COCC1.C(#N)C.C(O)(=O)C>[C:16]([C:18]1[CH:19]=[CH:20][C:21]([CH2:22][N:23]2[C:27]([CH2:28][N:12]3[CH2:11][CH2:10][C:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([CH3:2])[CH:4]=4)([OH:15])[CH2:14][CH2:13]3)=[CH:26][N:25]=[CH:24]2)=[CH:30][CH:31]=1)#[N:17]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 5003444Sodium cyanoborohydrideHCID 106322894-[(5-Formylimidazol-1-yl)methyl]benzonitrileHCID 211931674-(3-Methylphenyl)-4-hydroxypiperidine hydrochloride

Product 1

HCID 9864999N-{[1-(4-Cyanobenzyl)-1H-imidazol-5-yl]methyl}-4-(3-methylphenyl)-4 hydroxy piperidine

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 4-(3-methylphenyl)-4-hydroxypiperidine hydrochloride (457 mg, 2.00 mmol), the aldehyde from step E (508 mg, 2.41 mmol), and 3A molecular sieves (2.0 g) in methanol (20 ml) was added sodium cyanoborohydride (2.20 ml of a 1M solution in THF, 2.20 mmol). The pH was adjusted to 5 by addition of acetic acid and the reaction stirred under argon for 48 hrs at room temperature. The solids were removed by filtration and the filtrate partitioned between EtOAc and saturated NaHCO3 solution, the organic extracts were dried (MgSO4), and the solvent evaporated in vacuo. The residue was purified by chromatography (SiO2, gradient elution, 5 to 7% MeOH in methylene chloride. The residue was converted to the corresponding hydrochloride salt by its treatment with a solution of two equivalents of HCl in aqueous acetonitrile and subsequent evaporation of solvents in vacuo.

Workup

  1. customThe solids were removed by filtration
  2. customthe filtrate partitioned between EtOAc and saturated NaHCO3 solution
  3. dry with materialthe organic extracts were dried (MgSO4)
  4. customthe solvent evaporated in vacuo
  5. customThe residue was purified by chromatography (
  6. washSiO2, gradient elution, 5 to 7% MeOH in methylene chloride

Sources & evidence

ORD record
ord-4183012c0a2544628e0d31fc6685767c
Source dataset
uspto-grants-1999_04
Patent number
US05891889

Reaction notes

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