Methyl Isobutyl Ketone → trans-3-methoxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-4-[[3-(trifluoromethyl)benzoyl]amino]-1-piperidinebutanamide

HRID 981313Notes

Reaction equation

HRID 981313 reaction equation
[CH3:1][O:2][C@H:3]1[C@H:8]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[CH2:7][CH2:6][NH:5][CH2:4]1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C.[Br-].[CH3:36][CH:37]1[O:41][C:40](=[N+:42]([CH3:44])[CH3:43])[C:39]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:38]1>O>[CH3:1][O:2][C@H:3]1[C@H:8]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:18])[F:19])[CH:12]=2)[CH2:7][CH2:6][N:5]([CH:37]([CH3:36])[CH2:38][C:39]([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:40]([N:42]([CH3:43])[CH3:44])=[O:41])[CH2:4]1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 20071674N-(dihydro-5-methyl-3,3-diphenyl-2(3H)-furanylidene)-N-methylmethanaminium bromideHCID 67928786trans-N-(3-methoxy-4-piperidinyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 131716779trans-3-methoxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-4-[[3-(trifluoromethyl)benzoyl]amino]-1-piperidinebutanamideYield 22.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 3.0 parts of trans-N-(3-methoxy-4-piperidinyl)-3-(trifluoromethyl)benzamide, 2.65 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone was stirred for 30 minutes at reflux temperature, using a water separator. After cooling 3.96 parts of N-(dihydro-5-methyl-3,3-diphenyl-2(3H)-furanylidene)-N-methylmethanaminium bromide were added and stirring was continued for 5 hours at reflux. After cooling overnight at room temperature, the reaction mixture was washed twice with 50 parts of water, dried, filtered and evaporated in vacuo. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 8 parts of acetonitrile. The product was filtered off and dried, yielding 1.3 parts (22.5%) of trans-3-methoxy-N,N,γ-trimethyl-α,α-diphenyl-4-[[3-(trifluoromethyl)benzoyl]amino]-1-piperidinebutanamide; mp. 197.8° C. (compound 52).

Workup

  1. temperatureat reflux temperature
  2. additionwere added
  3. stirringstirring
  4. waitwas continued for 5 hours
  5. temperatureat reflux
  6. washthe reaction mixture was washed twice with 50 parts of water
  7. customdried
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue was purified by column chromatography over silica gel using
  11. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  12. customThe pure fractions were collected
  13. customthe eluent was evaporated
  14. customThe residue was crystallized from 8 parts of acetonitrile
  15. filtrationThe product was filtered off
  16. customdried

Sources & evidence

ORD record
ord-e28060d469d34850b2d695b0b684ef29
Source dataset
uspto-grants-1991_02
Patent number
US04990521

Reaction notes

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