Potassium Hydroxide → cis-5-amino-4-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide

HRID 981305Notes

Reaction equation

HRID 981305 reaction equation
[NH2:1][C:2]1[C:3]([Cl:26])=[CH:4][C:5]([O:24][CH3:25])=[C:6]([CH:23]=1)[C:7]([NH:9][C@H:10]1[CH2:15][CH2:14][N:13](C(OCC)=O)[CH2:12][C@H:11]1[O:21][CH3:22])=[O:8].[OH-].[K+]>CC(O)C>[NH2:1][C:2]1[C:3]([Cl:26])=[CH:4][C:5]([O:24][CH3:25])=[C:6]([CH:23]=1)[C:7]([NH:9][C@H:10]1[CH2:15][CH2:14][NH:13][CH2:12][C@H:11]1[O:21][CH3:22])=[O:8]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 67928779Ethyl cis-4-[(5-amino-4-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinecarboxylate

Product 1

HCID 67928757cis-5-amino-4-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamideYield 85%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 81 parts of ethyl cis-4-[(5-amino-4-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinecarboxylate, 122 parts of potassium hydroxide and 800 parts of 2-propanol was stirred for 6 hours at reflux temperature. The whole was stirred overnight at room temperature. The reaction mixture was evaporated. The residue was taken up in water and heated for a while. The mixture was evaporated again. The residue was taken up in water and the aqueous phase was extracted twice with dichloromethane. The combined organic layers were washed with water, dried, filtered and evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 58 parts (85%) of cis-5-amino-4-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide; mp. 191.8° C. (interm. 15).

Workup

  1. temperatureat reflux temperature
  2. stirringThe whole was stirred overnight at room temperature
  3. customThe reaction mixture was evaporated
  4. temperatureheated for a while
  5. customThe mixture was evaporated again
  6. extractionthe aqueous phase was extracted twice with dichloromethane
  7. washThe combined organic layers were washed with water
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was crystallized from acetonitrile
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-08adba1b67ed496887f8cf85efdba8f7
Source dataset
uspto-grants-1991_02
Patent number
US04990521

Reaction notes

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