Sodium ethoxide → Ethyl 4-[5-(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate

HRID 1459460Notes

Reaction equation

HRID 1459460 reaction equation
Cl.[NH2:2][C:3](=[N:15][OH:16])[CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5]1.[O-]CC.[Na+].[NH2:21][C:22]1[C:27]2[CH2:28][CH2:29][O:30][C:26]=2[C:25]([C:31](OC)=O)=[CH:24][C:23]=1[Cl:35]>C(O)C>[NH2:21][C:22]1[C:27]2[CH2:28][CH2:29][O:30][C:26]=2[C:25]([C:31]2[O:16][N:15]=[C:3]([CH:4]3[CH2:5][CH2:6][N:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:8][CH2:9]3)[N:2]=2)=[CH:24][C:23]=1[Cl:35]

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 54393661Methyl 4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylateHCID 86753480Ethyl 4-[amino(hydroxyimino)methyl]-1-piperidine-carboxylate hydrochloride

Product 1

HCID 54520153Ethyl 4-[5-(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of intermediate 2 (10.07 g), sodium ethoxide (5.42 g) and molecular sieves (45 g) in ethanol (150 ml) was stirred for 30 minutes at RT. Intermediate 1 (9.1 g) was added and the reaction mixture was stirred and refluxed for 10 hours. The reaction mixture was cooled, filtered and the filtrate evaporated. The residue was purified by column chromatography on silica gel (eluent: CH2Cl2 /CH3OH 95/5). The pure fractions were collected and the solvent evaporated, yielding 11.6 g (74%) of ethyl 4- [5-(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)- 1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate (intermediate 3; mp. 162.4° C.).

Workup

  1. stirringthe reaction mixture was stirred
  2. temperaturerefluxed for 10 hours
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered
  5. customthe filtrate evaporated
  6. customThe residue was purified by column chromatography on silica gel (eluent: CH2Cl2 /CH3OH 95/5)
  7. customThe pure fractions were collected
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-2e24f6f4809948109cd7b5af270e2f54
Source dataset
uspto-grants-1998_12
Patent number
US05854261

Reaction notes

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