Hydrochloric Acid → Ethyl 4-{4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl}-alpha,alpha-dimethylbenzeneacetate hydrochloride

HRID 1266622Notes

Reaction equation

HRID 1266622 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:9][CH:8]=1)=[O:6].[C:21]1([C:27]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[OH:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>C1(C)C(C)=CC=CC=1>[ClH:1].[OH:28][C:27]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH:29]1[CH2:34][CH2:33][N:32]([CH2:2][CH2:3][CH2:4][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([CH3:20])([CH3:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:9][CH:8]=2)=[O:6])[CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 15723AzacyclonolHCID 11231785Ethyl 4-(4-chloro-1-oxobutyl)-alpha,alpha-dimethylbenzeneacetate

Product 1

HCID 12939646Ethyl 4-{4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl}-alpha,alpha-dimethylbenzeneacetate hydrochlorideYield 70.5%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent2×

Procedure

Dissolve 2-[4-(4-chloro-butyryl)-phenyl]-2-methyl-propionic acid, ethyl ester (15.0 g, 49.53 mmol) and α,α-diphenyl-4-piperidinemethanol (29.66 g, 106.4 mmol) in xylene (60 mL). Reflux for 5.5 hours, cool in an ice bath, filter and wash with cold xylenes (25 mL). Filter the filtrate though silica gel (20 g) and wash the gel with xylenes (40 mL). Add xylene (60 mL) and concentrated hydrochloric acid (6.45 g, 65.6 mmol) with stirring. Add additional xylenes (40 mL) and stir for 2 hour. Filter, wash with xylene (50 mL), vacuum dry and slurry with a mixture of ethanol (60 mL) and hexane (120 mL) at 70-72° C. for 30 minutes. Filter, wash with 3:1 v/v solution of n-heptane/ethanol (30 mL) and dry to give the title compound as a light white solid (19.7 g, 70%); mp 206-208° C.

Workup

  1. temperatureReflux for 5.5 hours
  2. temperaturecool in an ice bath
  3. filtrationfilter
  4. washwash with cold xylenes (25 mL)
  5. filtrationFilter the filtrate though silica gel (20 g)
  6. washwash the gel with xylenes (40 mL)
  7. filtrationFilter
  8. washwash with xylene (50 mL), vacuum
  9. customdry
  10. additionslurry with a mixture of ethanol (60 mL) and hexane (120 mL) at 70-72° C. for 30 minutes
  11. filtrationFilter
  12. washwash with 3:1 v/v solution of n-heptane/ethanol (30 mL)
  13. customdry

Sources & evidence

ORD record
ord-9844415ed70744b8983f115472d70efb
Source dataset
uspto-grants-2003_04
Patent number
US06548675B2

Reaction notes

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