Triethylamine → Ethyl cis-4-[(4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofuranyl)carbonylamino]-3-methoxy-1-piperidinecarboxylate

HRID 441142Notes

Reaction equation

HRID 441142 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:13]([OH:15])=O)[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1.ClC(OCC)=O.[NH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][CH:24]1[O:34][CH3:35].C([N:38](CC)CC)C>ClC(Cl)Cl>[NH2:38][C:12]1[C:6]2[CH2:7][C:8]([CH3:10])([CH3:11])[O:9][C:5]=2[C:4]([C:13]([NH:22][C@H:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][C@H:24]2[O:34][CH3:35])=[O:15])=[CH:3][C:2]=1[Cl:1]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 3019430Ethyl 4-amino-3-methoxypiperidine-1-carboxylateHCID 101769185-Chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxylic acid

Product 1

HCID 15296155Ethyl cis-4-[(4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofuranyl)carbonylamino]-3-methoxy-1-piperidinecarboxylateYield 93.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Conditions

Temperature
10 °C

Procedure

To a solution of 8.1 parts of 4-amino, 5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxylic acid in 218 parts of trichloromethane and 3.43 parts of N,N-diethylethanamine were added dropwise 3.63 parts of ethyl chloroformate, keeping the temperature below 10° C. After stirring for 1/2 hour at 10° C., the whole was added to a solution of 6.26 parts of ethyl 4-amino-3-methoxy-1-piperidinecarboxylate in 145 parts of trichloromethane at 10° C. Stirring was continued for 1/2 hour at room temperature. The reaction mixture was washed with Water, NaOH 5% and water and was then dried, filtered and evaporated. The residue was suspended in 2,2'-oxybispropane. The product was filtered off and dried, yielding 12.3 parts (93.2%) of ethyl cis-4-[(4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofuranyl)carbonylamino]-3-methoxy-1-piperidinecarboxylate (interm. 1).

Workup

  1. customthe temperature below 10° C
  2. stirringStirring
  3. waitwas continued for 1/2 hour at room temperature
  4. washThe reaction mixture was washed with Water, NaOH 5% and water
  5. customwas then dried
  6. filtrationfiltered
  7. customevaporated
  8. filtrationThe product was filtered off
  9. customdried

Sources & evidence

ORD record
ord-b2ab2212486b4553af37a60cd1068089
Source dataset
uspto-grants-1996_05
Patent number
US05521314

Reaction notes

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