Nitric Acid → Ethyl 5-methoxy-4-((1-methylpiperidin-4-yl)methoxy)-2-nitrobenzoate

HRID 2233254Notes

Reaction equation

HRID 2233254 reaction equation
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:18]=[CH:19][C:20]=1[O:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]1)[C:13]([O:15][CH2:16][CH3:17])=[O:14].[N+:30]([O-])([OH:32])=[O:31]>ClCCl>[CH3:8][O:9][C:10]1[CH:11]=[C:12]([C:18]([N+:30]([O-:32])=[O:31])=[CH:19][C:20]=1[O:21][CH2:22][CH:23]1[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]1)[C:13]([O:15][CH2:16][CH3:17])=[O:14]

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 6422Trifluoroacetic acidHCID 21874826Ethyl 3-methoxy-4-((1-methylpiperidin-4-yl)methoxy)benzoate

Product 1

HCID 21874808Ethyl 5-methoxy-4-((1-methylpiperidin-4-yl)methoxy)-2-nitrobenzoateYield 90.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trifluoroacetic acid (37.5 ml) was added to a solution of ethyl 3-methoxy-4-(1-methylpiperidin-4-ylmethoxy)benzoate (30.6 g, 89 mmol) in dichloromethane (75 ml) at 0-5° C. before dropwise addition of a solution of fuming nitric acid (7.42 ml, 178 mmol) in dichloromethane (15 ml) over 15 minutes. The reaction was stirred at ambient temperature for 2 hours, the volatiles were removed in vacuo and the residue was dissolved in dichloromethane (50 ml). The solution was cooled to 0-5° C., diethyl ether was added (50 ml) and the resultant precipitate was collected by suction filtration, and dried in vacuo. The solid was taken up in dichloromethane (500 ml), 3.0N hydrogen chloride in diethyl ether (30 ml) was added followed by diethyl ether (500 ml) which cause precipitation of a solid. Collection of the solid by suction filtration followed by drying in vacuo yielded ethyl 3-methoxy-4-(1-methylpiperidin-4-ylmethoxy)-6-nitrobenzoate (28.4 g, 82% yield) as a white solid:

Workup

  1. customthe volatiles were removed in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane (50 ml)
  3. temperatureThe solution was cooled to 0-5° C.
  4. additiondiethyl ether was added (50 ml)
  5. filtrationthe resultant precipitate was collected by suction filtration
  6. customdried in vacuo
  7. addition3.0N hydrogen chloride in diethyl ether (30 ml) was added
  8. customprecipitation of a solid
  9. customCollection of the solid
  10. filtrationby suction filtration
  11. customby drying in vacuo

Sources & evidence

ORD record
ord-95ff5ffc1cf94cedad90662fcee51e73
Source dataset
uspto-grants-2010_05
Patent number
US07709479B1

Reaction notes

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