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

HRID 1735185Notes

Reaction equation

HRID 1735185 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][C:9]([CH3:12])([CH3:11])[O:10][C:6]=2[C:5]([C:13]([OH:15])=O)=[CH:4][C:3]=1[Cl:16].ClC(OCC)=O.[NH2:23][CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][CH:25]1[O:35][CH3:36]>ClC(Cl)Cl.C(N(CC)CC)C>[NH2:1][C:2]1[C:7]2[CH2:8][C:9]([CH3:11])([CH3:12])[O:10][C:6]=2[C:5]([C:13]([NH:23][C@H:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:26][C@H:25]2[O:35][CH3:36])=[O:15])=[CH:4][C:3]=1[Cl:16]

Participants

6

Reactant 3

HCID 10928Ethyl chloroformateHCID 3019430Ethyl 4-amino-3-methoxypiperidine-1-carboxylateHCID 106577584-Amino-5-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 2

HCID 6212ChloroformSolvent2×HCID 8471TriethylamineSolvent

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-bddf8607b9774f9bb87003af9928933c
Source dataset
uspto-grants-1996_07
Patent number
US05536733

Reaction notes

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