Phenol → N-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dimethyl-5-nitro-6-phenoxypyridin-4-amine

HRID 2121664Notes

Reaction equation

HRID 2121664 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][NH:25][C:26]2[C:31]([CH3:32])=[C:30]([CH3:33])[N:29]=[C:28](Cl)[C:27]=2[N+:35]([O-:37])=[O:36])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[O-]C1C=CC=CC=1>COCCOCCOC>[CH2:10]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][NH:25][C:26]2[C:27]([N+:35]([O-:37])=[O:36])=[C:28]([O:9][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[N:29]=[C:30]([CH3:33])[C:31]=2[CH3:32])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 24758Sodium hydrideHCID 119047PhenolateHCID 21973806N-[2-(1-benzylpiperidin-4-yl)ethyl]-2-chloro-5,6-dimethyl-3-nitropyridin-4-amine

Product 1

HCID 21973847N-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dimethyl-5-nitro-6-phenoxypyridin-4-amineYield 47.2%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent2×

Procedure

Sodium hydride (1.196 g of 60%, 29.9 mmol) was added to a solution of phenol (2.81 g, 29.9 mol) in diglyme (40 mL). The mixture was stirred for 15 minutes after the cessation of gas evolution. A solution of N-[2-(1-benzylpiperidin-4-yl)ethyl]-2-chloro-5,6-dimethyl-3-nitropyridin-4-amine (10.9 g, 27.2 mmol) in hot diglyme was added to the phenoxide mixture. The reaction mixture was heated at reflux for 1.5 hours, cooled to ambient temperature, and then concentrated to remove the diglyme (60° C. bath, 21 Pa). The residue was purified by column chromatography eluting first with 1% methanol in dichloromethane to elute residual diglyme and then with 5% methanol in dichloromethane to remove product. The fractions were concentrated to provide 5.91 g of N-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dimethyl-5-nitro-6-phenoxypyridin-4-amine as an orange-brown oil which solidified on standing.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1.5 hours
  3. concentrationconcentrated
  4. customto remove the diglyme (60° C. bath, 21 Pa)
  5. customThe residue was purified by column chromatography
  6. washeluting first with 1% methanol in dichloromethane
  7. washto elute residual diglyme
  8. customwith 5% methanol in dichloromethane to remove product
  9. concentrationThe fractions were concentrated

Sources & evidence

ORD record
ord-80924559864b47baa838ff665544df87
Source dataset
uspto-grants-2004_02
Patent number
US06696465B2

Reaction notes

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