Methyl 5-{[(4-nitrophenoxy)carbonyl]oxy}nicotinate → Methyl 5-[{(4-[2-(3-{[(2-bromoethyl)amino]carbonyl}phenyl)ethyl]piperidin-1-yl}carbonyl)oxy]nicotinate

HRID 2074252Notes

Reaction equation

HRID 2074252 reaction equation
Cl.[Br:2][CH2:3][CH2:4][NH:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][CH2:14][CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH:8]=1.[N+](C1C=CC([O:29][C:30]([O:32][C:33]2[CH:34]=[N:35][CH:36]=[C:37]([CH:42]=2)[C:38]([O:40][CH3:41])=[O:39])=O)=CC=1)([O-])=O>C(#N)C>[Br:2][CH2:3][CH2:4][NH:5][C:6]([C:7]1[CH:8]=[C:9]([CH2:13][CH2:14][CH:15]2[CH2:20][CH2:19][N:18]([C:30]([O:32][C:33]3[CH:34]=[N:35][CH:36]=[C:37]([CH:42]=3)[C:38]([O:40][CH3:41])=[O:39])=[O:29])[CH2:17][CH2:16]2)[CH:10]=[CH:11][CH:12]=1)=[O:21]

Participants

4

Reactant 2

HCID 57421835Methyl 5-{[(4-nitrophenoxy)carbonyl]oxy}nicotinateHCID 57421836N-(2-bromoethyl)-3-(2-piperidin-4-ylethyl)benzamide hydrochloride

Product 1

HCID 57507765Methyl 5-[{(4-[2-(3-{[(2-bromoethyl)amino]carbonyl}phenyl)ethyl]piperidin-1-yl}carbonyl)oxy]nicotinateYield 46%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

TEA (0.90 ml) was dropwise added to an acetonitrile (30 ml) suspension of N-(2-bromoethyl)-3-(2-piperidin-4-ylethyl)benzamide hydrochloride (1.20 g) and methyl 5-{[(4-nitrophenoxy)carbonyl]oxy}nicotinate (1.02 g), followed by stirring overnight at room temperature. The reaction solvent was evaporated under reduced pressure, then aqueous saturated sodium hydrogencarbonate solution was added thereto, extracted with EtOAc, and dried over anhydrous magnesium sulfate. This was filtered, the solvent was evaporated, and the residue was purified two times through silica gel column chromatography (basic silica with eluent: hexane:EtOAc=1:2 (v/v), next neutral silica with eluent: chloroform:methanol=19:1 (v/v)) to obtain methyl 5-[{(4-[2-(3-{[(2-bromoethyl)amino]carbonyl}phenyl)ethyl]piperidin-1-yl}carbonyl)oxy]nicotinate (762 mg) as a white powder.

Workup

  1. customThe reaction solvent was evaporated under reduced pressure
  2. additionaqueous saturated sodium hydrogencarbonate solution was added
  3. extractionextracted with EtOAc
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThis was filtered
  6. customthe solvent was evaporated
  7. customthe residue was purified two times through silica gel column chromatography (basic silica with eluent: hexane:EtOAc=1:2 (v/v), next neutral silica with eluent: chloroform:methanol=19:1 (v/v))

Sources & evidence

ORD record
ord-4d2e79b8c83b4413a9babc7d26f6be73
Source dataset
uspto-grants-2011_04
Patent number
US07919494B2

Reaction notes

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