Azacyclonol → Methyl 2-(4-(4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butanoyl)phenyl)-2-methylpropanoate hydrochloride

HRID 411919Notes

Reaction equation

HRID 411919 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:19])([CH3:18])[C:14]([O:16][CH3:17])=[O:15])=[CH:9][CH:8]=1)=[O:6].[C:20]1([C:26]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[OH:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1(C)C=CC=CC=1>[ClH:1].[OH:27][C:26]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)[CH:28]1[CH2:33][CH2:32][N:31]([CH2:2][CH2:3][CH2:4][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([CH3:19])([CH3:18])[C:14]([O:16][CH3:17])=[O:15])=[CH:9][CH:8]=2)=[O:6])[CH2:30][CH2:29]1

Participants

4

Reactant 2

HCID 15723AzacyclonolHCID 10062338Methyl 4-(4-chloro-1-oxobutyl)-alpha,alpha-dimethylbenzeneacetate

Product 1

HCID 22471930Methyl 2-(4-(4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butanoyl)phenyl)-2-methylpropanoate hydrochlorideYield 76.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Dissolve 2-[4-(4-chloro-butyryl)-phenyl]-2-methyl-propionic acid, methyl ester (2.82 g, 10.0 mmol) and α,α-diphenyl-4-piperidinemethanol (5.58 g, 21.0 mmol) in toluene (20 mL). Reflux for 29 hours, cool in an ice bath, filter, filter the filtrate though silica gel (5 g) and wash the gel with toluene (10 mL). Evaporate the solvent in vacuo and dissolve the residue in ethyl ether (100 mL). Add anhydrous hydrogen chloride and filter to give the title compound as an off-white powder (4.2 g, 76%); mp 165-175° C.

Workup

  1. temperatureReflux for 29 hours
  2. temperaturecool in an ice bath
  3. filtrationfilter
  4. filtrationfilter the filtrate though silica gel (5 g)
  5. washwash the gel with toluene (10 mL)
  6. customEvaporate the solvent in vacuo
  7. dissolutiondissolve the residue in ethyl ether (100 mL)
  8. filtrationAdd anhydrous hydrogen chloride and filter

Sources & evidence

ORD record
ord-5b828f2ebb914fa48eccb0905a8950f1
Source dataset
uspto-grants-2003_05
Patent number
US06559312B2

Reaction notes

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