Acetic Acid → trans-4-[(4-amino-5-cyano-2-hydroxybenzoyl)amino]-3-hydroxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide monohydrate

HRID 981310Notes

Reaction equation

HRID 981310 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([CH:8]([CH3:28])[CH2:9][C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH2:4][C@H:3]1[OH:29].[NH2:30][C:31]1[C:39]([C:40]#[N:41])=[CH:38][C:34]([C:35](O)=[O:36])=[C:33]([OH:42])[CH:32]=1.ClC(Cl)Cl.C(O)(=O)C>O>[OH2:12].[NH2:30][C:31]1[C:39]([C:40]#[N:41])=[CH:38][C:34]([C:35]([NH:1][C@@H:2]2[CH2:7][CH2:6][N:5]([CH:8]([CH3:28])[CH2:9][C:10]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:11]([N:13]([CH3:15])[CH3:14])=[O:12])[CH2:4][C@H:3]2[OH:29])=[O:36])=[C:33]([OH:42])[CH:32]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6212ChloroformHCID 125651974-Amino-5-cyano-2-hydroxybenzoic acidHCID 67928771trans-4-amino-3-hydroxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide

Product 1

HCID 86744576trans-4-[(4-amino-5-cyano-2-hydroxybenzoyl)amino]-3-hydroxy-N,N,gamma-trimethyl-alpha,alpha-diphenyl-1-piperidinebutanamide monohydrateYield 10%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred solution of 3.95 parts of trans-4-amino-3-hydroxy-N,N,γ-trimethyl-α,α-diphenyl-1-piperidinebutanamide and 1.78 parts of 4-amino-5-cyano-2-hydroxybenzoic acid in 150 parts of trichloromethane were added 3.1 parts of N,N'-methanetetraylbis[cyclohexanamine] and stirring was continued over weekend at room temperature. The reaction mixture was acidified with an acetic acid solution in water. The separated organic layer was washed with water, dried, filtered and evaporated. The residue was taken up in acetonitrile and the precipitate was filtered off. The filtrate was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 0.55 parts (10%) of trans-4-[(4-amino-5-cyano-2-hydroxybenzoyl)amino]-3-hydroxy-N,N,γ-trimethyl-α,α-diphenyl-1-piperidinebutanamide monohydrate; mp. 211.4° C. (compound 42).

Workup

  1. waitwas continued over weekend at room temperature
  2. washThe separated organic layer was washed with water
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. filtrationthe precipitate was filtered off
  7. customThe filtrate was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from acetonitrile
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-164e874d7f5c482bae378881628d9c8f
Source dataset
uspto-grants-1991_02
Patent number
US04990521

Reaction notes

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