Potassium Hydroxide → 5-Chloro-2,3-dihydro-7-[3-(4-piperidinyl)-1,2,4-oxadiazol-5-yl]-4-benzofuranamine

HRID 1459461Notes

Reaction equation

HRID 1459461 reaction equation
[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]2[O:15][N:14]=[C:13]([CH:16]3[CH2:21][CH2:20][N:19](C(OCC)=O)[CH2:18][CH2:17]3)[N:12]=2)=[CH:4][C:3]=1[Cl:27].[OH-].[K+]>CC(O)C>[Cl:27][C:3]1[C:2]([NH2:1])=[C:7]2[CH2:8][CH2:9][O:10][C:6]2=[C:5]([C:11]2[O:15][N:14]=[C:13]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[N:12]=2)[CH:4]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 54520153Ethyl 4-[5-(4-amino-5-chloro-2,3-dihydro-7-benzofuranyl)-1,2,4-oxadiazol-3-yl]-1-piperidinecarboxylate

Product 1

HCID 538340175-Chloro-2,3-dihydro-7-[3-(4-piperidinyl)-1,2,4-oxadiazol-5-yl]-4-benzofuranamineYield 64%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of intermediate 3 (10 g) and potassium hydroxide (14 g) in 2-propanol (200 ml) was stirred and refluxed for 6 hours. The reaction mixture was cooled and the solvent evaporated. Water was added to the residue and evaporated again. The residue was stirred in water and the resulting precipitate was filtered off, washed with water and purified by column chromatography on silica gel (eluent: CH2Cl2 /(CH3 OH/NH3) 90/10). The pure fractions were collected and the solvent evaporated, yielding 5.14 g (64%) of 5-chloro-2,3-dihydro-7-[3-(4-piperidinyl)-1,2,4-oxadiazol-5-yl]-4-benzofuranamine (intermediate 4; mp. 219.0° C.).

Workup

  1. temperaturerefluxed for 6 hours
  2. temperatureThe reaction mixture was cooled
  3. customthe solvent evaporated
  4. additionWater was added to the residue
  5. customevaporated again
  6. stirringThe residue was stirred in water
  7. filtrationthe resulting precipitate was filtered off
  8. washwashed with water
  9. custompurified by column chromatography on silica gel (eluent: CH2Cl2 /(CH3 OH/NH3) 90/10)
  10. customThe pure fractions were collected
  11. customthe solvent evaporated

Sources & evidence

ORD record
ord-8aef11a8fd604f708d8bf66beddfaf94
Source dataset
uspto-grants-1998_12
Patent number
US05854261

Reaction notes

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