Phenol → 3-Dimethylaminomethyl-4-(3-hydroxy-phenyl)-1-(1-phenyl-cyclohexyl)-piperidin-4-ol Dihydrochloride

HRID 1825854Notes

Reaction equation

HRID 1825854 reaction equation
COC.C1(O)C=CC=CC=1.[ClH:11].Cl.[CH3:13][N:14]([CH2:16][CH:17]1[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30]C)[CH:25]=2)([OH:23])[CH2:21][CH2:20][N:19]([C:32]2([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH2:18]1)[CH3:15].[H-].C([Al+]CCCC)CCC>C1(C)C=CC=CC=1.C(O)C.C(OCC)(=O)C>[ClH:11].[ClH:11].[CH3:15][N:14]([CH2:16][CH:17]1[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)([OH:23])[CH2:21][CH2:20][N:19]([C:32]2([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH2:18]1)[CH3:13]

Participants

8

Reactant 4

HCID 996PhenolHCID 8254Dimethyl EtherHCID 103003283-Dimethylaminomethyl-4-(3-methoxyphenyl)-1-(1-phenyl-cyclohexyl)-piperidin-4-ol DihydrochlorideHCID 21879971Dibutylaluminium hydride

Product 1

HCID 101843763-Dimethylaminomethyl-4-(3-hydroxy-phenyl)-1-(1-phenyl-cyclohexyl)-piperidin-4-ol Dihydrochloride

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The synthesis instructions are described analogously to Example 6, except for the last step. The methyl ether was then cleaved into the phenol. To that end, 0.5 g (1.2 mmol.) of the free base of compound (6) was dissolved in 5 ml of toluene, and 10 ml of dibutylaluminium hydride solution (1.5 M in toluene) were added at 0° C. and under a nitrogen atmosphere. After 12 hours' stirring, the batch was hydrolysed with 5 ml of ethyl acetate and 5 ml of ethanol, the solvent was removed in vacuo, the residue was dissolved in methyl ethyl ketone, and 1.0 ml of trimethylsilyl chloride was added thereto. The yield of (11) was 71 mg (0.15 mmol., 12%). The compound melted between 245 and 248° C.

Workup

  1. customThe synthesis instructions
  2. customthe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in methyl ethyl ketone
  4. addition1.0 ml of trimethylsilyl chloride was added
  5. custommelted between 245 and 248° C.

Sources & evidence

ORD record
ord-0e8859431aa04844a73163ab62f9a641
Source dataset
uspto-grants-2006_05
Patent number
US07049327B2

Reaction notes

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