4-Fluorobenzohydrazide → Pyridin-3-yl 4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylate

HRID 222253

Reaction equation

HRID 222253 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]2)=[O:9])[CH:2]=1.[F:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([NH:26][NH2:27])=O)=[CH:22][CH:21]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[F:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]2[O:18][C:16]([CH:13]3[CH2:12][CH2:11][N:10]([C:8]([O:7][C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[O:9])[CH2:15][CH2:14]3)=[N:27][N:26]=2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 99724-FluorobenzohydrazideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 574218421-[(Pyridin-3-yloxy)carbonyl]piperidine-4-carboxylic acid

Product 1

HCID 58270699Pyridin-3-yl 4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylateYield 50.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-[(pyridin-3-yloxy)carbonyl]piperidine-4-carboxylic acid (300 mg), 4-fluorobenzohydrazide (222 mg), HOBt (170 mg), and DCM (6 mL) was added WSC hydrochloride (299 mg), followed by stirring at room temperature overnight. The reaction liquid was purified directly by silica gel column chromatography (chloroform/methanol=99/1 to 90/10). The residue was dissolved in THF (6 mL), and toluenesulfonyl chloride (686 mg) and triethylamine (1.0 mL) were added thereto, followed by stirring at 50° C. for 8 hours. The reaction liquid was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30 to 0/100). To the purified product were added isopropanol/water, and the resulting solid was collected by filtration and dried to obtain pyridin-3-yl 4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylate (224 mg) as a colorless solid.

Workup

  1. customThe reaction liquid
  2. customwas purified directly by silica gel column chromatography (chloroform/methanol=99/1 to 90/10)
  3. dissolutionThe residue was dissolved in THF (6 mL)
  4. additiontoluenesulfonyl chloride (686 mg) and triethylamine (1.0 mL) were added
  5. stirringby stirring at 50° C. for 8 hours
  6. customThe reaction liquid
  7. concentrationwas concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=70/30 to 0/100)
  9. additionTo the purified product were added isopropanol/water
  10. filtrationthe resulting solid was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-4f7d6f9073cf4b039f22d2e354f7e8eb
Source dataset
uspto-grants-2012_06
Patent number
US08207199B2

Linked notes

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