4-[5-(4-Methanesulfonylphenyl)-2,3-dihydrobenzofuran-2-yl]piperidine-1-carbonitrile → 1-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-4-[5-(4-methanesulfonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine

HRID 1622251Notes

Reaction equation

HRID 1622251 reaction equation
[OH:1][NH:2][C:3](=[NH:7])[CH:4]([CH3:6])[CH3:5].[CH3:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:19]=[CH:20][C:21]3[O:25][CH:24]([CH:26]4[CH2:31][CH2:30][N:29]([C:32]#N)[CH2:28][CH2:27]4)[CH2:23][C:22]=3[CH:34]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH:4]([C:3]1[N:7]=[C:32]([N:29]2[CH2:28][CH2:27][CH:26]([CH:24]3[CH2:23][C:22]4[CH:34]=[C:18]([C:15]5[CH:16]=[CH:17][C:12]([S:9]([CH3:8])(=[O:11])=[O:10])=[CH:13][CH:14]=5)[CH:19]=[CH:20][C:21]=4[O:25]3)[CH2:31][CH2:30]2)[O:1][N:2]=1)([CH3:6])[CH3:5]

Participants

6

Reactant 2

HCID 866756724-[5-(4-Methanesulfonylphenyl)-2,3-dihydrobenzofuran-2-yl]piperidine-1-carbonitrileHCID 178449908HCID 178449908, compound

Product 1

HCID 712084321-(3-Isopropyl-[1,2,4]oxadiazol-5-yl)-4-[5-(4-methanesulfonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A 0.5 M solution of zinc chloride in tetrahydrofuran (0.78 mL) is diluted with tetrahydrofuran (5 mL) and added dropwise at room temperature to a mixture of N-hydroxy-isobutyramidine (40 mg) and 4-[5-(4-methanesulfonyl-phenyl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carbonitrile (100 mg) in ethyl acetate (5 mL). The reaction mixture is stirred at 50° C. for 4 h and cooled to room temperature. The precipitate is filtered off and heated to 100° C. for 2 h in a mixture of ethanol (5 mL) and glacial acetic acid (2.5 mL). The solvents are evaporated and the residue is mixed with dichloromethane and 10% aqueous K2CO3 solution. The organic phase is washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is triturated with diethyl ether to give the title compound. LC (method 2): tR=1.12 min; Mass spectrum (ESI+): m/z=468 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationThe precipitate is filtered off
  3. temperatureheated to 100° C. for 2 h in a mixture of ethanol (5 mL) and glacial acetic acid (2.5 mL)
  4. customThe solvents are evaporated
  5. additionthe residue is mixed with dichloromethane and 10% aqueous K2CO3 solution
  6. washThe organic phase is washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue is triturated with diethyl ether

Sources & evidence

ORD record
ord-50752ceb57374175adb0d9795d7e542e
Source dataset
uspto-grants-2014_07
Patent number
US08778926B2

Reaction notes

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