Potassium Hydroxide → 4-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamide

HRID 345597Notes

Reaction equation

HRID 345597 reaction equation
[NH2:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12](C(OCC)=O)[CH2:11][C@H:10]2[O:20][CH3:21])=[O:7])=[C:4]([O:25][CH3:26])[CH:3]=1.[OH-].[K+]>CC(O)C>[NH2:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[O:20][CH3:21])=[O:7])=[C:4]([O:25][CH3:26])[CH:3]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 11132816Ethyl cis-[4-(4-amino-5-chloro-2-methoxybenzamido)-3-methoxypiperidino]formate

Product 1

HCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamideYield 46%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 16.6 parts of cis-ethyl 4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-1-piperidinecarboxylate, 26.36 parts of potassium hydroxide and 160 parts of 2-propanol was stirred and refluxed for 3 hours. The reaction mixture was evaporated in vacuo on a boiling water-bath. Water was added to the residue and the whole was evaporated again. The residue was boiled in water on a warm water-bath. The precipitated product was filtered off and taken up in trichloromethane. The organic phase was separated, dried, filtered and evaporated. The residue was taken up in methylbenzene. The solid residue was filtered off and dried, yielding 6.7 parts (46%) of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4piperidinyl)benzamide; mp. 184.3° C. (compound 211).

Workup

  1. temperaturerefluxed for 3 hours
  2. customThe reaction mixture was evaporated in vacuo on a boiling water-bath
  3. additionWater was added to the residue
  4. customthe whole was evaporated again
  5. customThe residue was boiled in water on a warm water-bath
  6. filtrationThe precipitated product was filtered off
  7. customThe organic phase was separated
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. filtrationThe solid residue was filtered off
  12. customdried

Sources & evidence

ORD record
ord-5037a4da5fb34839b7fb2a7c30e8dde5
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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