Potassium Iodide → trans-4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-hydroxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide

HRID 981312Notes

Reaction equation

HRID 981312 reaction equation
[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[OH:15])=[O:7])=[C:4]([O:19][CH3:20])[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].[Br-].[CH3:30][CH:31]1[O:35][C:34](=[N+:36]([CH3:38])[CH3:37])[C:33]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:32]1>O.CC(C)CC(=O)C>[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][N:12]([CH:31]([CH3:30])[CH2:32][C:33]([C:45]3[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=3)([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:34]([N:36]([CH3:37])[CH3:38])=[O:35])[CH2:11][C@H:10]2[OH:15])=[O:7])=[C:4]([O:19][CH3:20])[CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 20071674N-(dihydro-5-methyl-3,3-diphenyl-2(3H)-furanylidene)-N-methylmethanaminium bromideHCID 67922711trans-4-amino-5-chloro-N-(3-hydroxy-4-piperidinyl)-2-methoxybenzamide

Product 1

HCID 131716778trans-4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-hydroxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamideYield 30.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 7909Methyl Isobutyl KetoneSolvent

Procedure

A mixture of 4.5 parts of trans-4-amino-5-chloro-N-(3-hydroxy-4-piperidinyl)-2-methoxybenzamide, 4 parts of sodium carbonate, 0.1 parts of potassium iodide and 120 parts of 4-methyl-2-pentanone was stirred for 1 hour at reflux using a water separator. 5.95 Parts of N-(dihydro-5-methyl-3,3-diphenyl-2(3H)-furanylidene)-N-methylmethanaminium bromide were added and stirring was continued for 1 hour at reflux. The organic layer was washed successively with water, a sodium carbonate solution in water and water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was dried in vacuo at 80° C., yielding 2.66 parts (30.6%) of trans-4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-hydroxy-N,N,γ-trimethyl-α,α-diphenyl-1-piperidinebutanamide; mp. 131.9° C. (compound 50).

Workup

  1. temperatureat reflux
  2. stirringstirring
  3. waitwas continued for 1 hour
  4. temperatureat reflux
  5. washThe organic layer was washed successively with water
  6. dry with materiala sodium carbonate solution in water and water, dried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was dried in vacuo at 80° C.

Sources & evidence

ORD record
ord-cd9f5509b37143b09e28def4b7a9ee31
Source dataset
uspto-grants-1991_02
Patent number
US04990521

Reaction notes

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