Triethylamine → Ethyl cis-[4-(4-amino-5-chloro-2-methoxybenzamido)-3-methoxypiperidino]formate

HRID 1440694Notes

Reaction equation

HRID 1440694 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1OC.C(N(CC)CC)C.Cl[C:22](OCC)=[O:23].[NH2:27][C@H:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][C@H:29]1[O:39][CH3:40]>O1CCCC1>[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([NH:27][C@H:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:30][C@H:29]2[O:39][CH3:40])=[O:8])=[C:4]([O:23][CH3:22])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 13677746Ethyl cis-(4-amino-3-methoxypiperidino)formateHCID 151645864-Amino-3-chloro-5-methoxybenzoic acid

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 33.3 g of 4-amino-5-chloro-3-methoxybenzoic acid, 27.0 ml of triethylamine, and 450 ml of tetrahydrofuran, 16.2 ml of ethyl chloroformate was added dropwise with stirring under ice-cooling. Stirring was continued for 1.5 hours under ice-cooling, a solution of 35.0 g of ethyl cis-(4-amino-3-methoxypiperidino)formate in 50 ml of tetrahydrofuran was added dropwise. After being stirred for 20 hours at room temperature, the reaction mixture was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with dichloromethane. The extract was washed with aqueous potassium carbonate solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was washed with diethyl ether to give 44.5 g of colorless crystals.

Workup

  1. additionwas added dropwise
  2. temperaturecooling
  3. stirringStirring
  4. temperaturecooling
  5. stirringAfter being stirred for 20 hours at room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. additionWater was added to the residue
  8. extractionthe mixture was extracted with dichloromethane
  9. washThe extract was washed with aqueous potassium carbonate solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. washThe residue was washed with diethyl ether

Sources & evidence

ORD record
ord-8b16be34c60b45eeb20d8cb0bdfcf621
Source dataset
uspto-grants-1996_03
Patent number
US05500422

Reaction notes

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