Acetonitrile → Methyl 5-[({4-[2-(3-cyanophenyl)ethyl]-1-piperidyl}carbonyl)oxy]nicotinate

HRID 2074336Notes

Reaction equation

HRID 2074336 reaction equation
[N+](C1C=CC(O[C:9]([O:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([CH:21]=2)[C:17]([O:19][CH3:20])=[O:18])=[O:10])=CC=1)([O-])=O.C(#N)C.Cl.[NH:28]1[CH2:33][CH2:32][CH:31]([CH2:34][CH2:35][C:36]2[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=2)[C:39]#[N:40])[CH2:30][CH2:29]1>CCOC(C)=O>[C:39]([C:38]1[CH:37]=[C:36]([CH2:35][CH2:34][CH:31]2[CH2:32][CH2:33][N:28]([C:9]([O:11][C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:21]=3)[C:17]([O:19][CH3:20])=[O:18])=[O:10])[CH2:29][CH2:30]2)[CH:43]=[CH:42][CH:41]=1)#[N:40]

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 574218243-[2-(4-Piperidyl)ethyl]benzonitrile hydrochlorideHCID 57421835Methyl 5-{[(4-nitrophenoxy)carbonyl]oxy}nicotinate

Product 1

HCID 57507814Methyl 5-[({4-[2-(3-cyanophenyl)ethyl]-1-piperidyl}carbonyl)oxy]nicotinateYield 38.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Methyl 5-{[(4-nitrophenoxy)carbonyl]oxy}nicotinate (723 mg) was added to an acetonitrile (10 ml) solution of 3-[2-(4-piperidyl)ethyl]benzonitrile hydrochloride (475 mg) and TEA (0.58 ml), followed by stirring overnight at room temperature. The reaction liquid was diluted with EtOAc, followed by washing with an aqueous saturated sodium hydrogencarbonate solution and drying over anhydrous magnesium sulfate. The solvent was evaporated, the resulting residue was subjected to basic silica gel column chromatography (eluent: hexane:EtOAc=1:1 (v/v)) and the side-product, nitrophenol was removed. Then, this was purified by silica gel column chromatography (eluent: hexane:EtOAc=3:2 (v/v)) to obtain methyl 5-[({4-[2-(3-cyanophenyl)ethyl]-1-piperidyl}carbonyl)oxy]nicotinate (284 mg).

Workup

  1. customThe reaction liquid
  2. washby washing with an aqueous saturated sodium hydrogencarbonate solution
  3. dry with materialdrying over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customthe side-product, nitrophenol was removed
  6. customThen, this was purified by silica gel column chromatography (eluent: hexane:EtOAc=3:2 (v/v))

Sources & evidence

ORD record
ord-6f41f4dd194a4b8f926a5dffc1719710
Source dataset
uspto-grants-2011_04
Patent number
US07919495B2

Reaction notes

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