Triethylamine → cis-Ethyl 4-(amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-1-piperidinecarboxylate

HRID 345596Notes

Reaction equation

HRID 345596 reaction equation
N[C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH3:13])[CH:3]=1.C(Cl)(=O)OCC.[NH2:20][C@H:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][C@H:22]1[O:32][CH3:33].C([N:36](CC)CC)C>ClC(Cl)Cl>[NH2:36][N:20]([C:6](=[O:8])[C:5]1[CH:9]=[C:10]([Cl:11])[CH:2]=[CH:3][C:4]=1[O:12][CH3:13])[C@H:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:23][C@H:22]1[O:32][CH3:33]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 13677746Ethyl cis-(4-amino-3-methoxypiperidino)formate

Product 1

HCID 131716645cis-Ethyl 4-(amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-1-piperidinecarboxylateYield 80%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a stirred solution of 22.5 parts of 4-amino-5-chloro-2-methoxybenzoic acid in 405 parts of trichloromethane were added dropwise successively 11.8 parts of N,N-diethylethanamine and 13 parts of ethyl carbonchloridate at a temperature below 10° C. Stirring was continued for 45 minutes at a temperature below 10° C. Then there was added dropwise a solution of 19.15 parts of cis-ethyl 4-amino-3-methoxy-1-piperidinecarboxylate in 360 parts of trichloromethane at the same temperature. Upon completion, stirring was continued for 18 hours at room temperature. The reaction mixture was washed successively three times with water, once with a 5% sodium hydroxide solution and again twice with water. The organic phase was dried, filtered and evaporated. The residue 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, yielding 29.3 parts (80%) of cis-ethyl 4-(amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-1 -piperidinecarboxylate as a residue (compound 168).

Workup

  1. stirringUpon completion, stirring
  2. waitwas continued for 18 hours at room temperature
  3. washThe reaction mixture was washed successively three times with water
  4. customThe organic phase was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue 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

Sources & evidence

ORD record
ord-db74ca1481354ddcb5d3405bb017964c
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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