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

HRID 238093Notes

Reaction equation

HRID 238093 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].C(O)(C(F)(F)F)=O.[N+:30]([O-])([OH:32])=[O:31]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([N+:30]([O-:32])=[O:31])=[CH:12][C:13]=1[O:14][CH2:15][CH:16]1[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]1)[C:6]([O:8][CH2:9][CH3:10])=[O:7]

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

A solution of ethyl 3-methoxy-4-(1-methylpiperidin-4-ylmethoxy)benzoate (30.6 g, 89 mmol) in methylene chloride (75 ml) was cooled to 0-5° C. TFA (37.5 ml) was added followed by the dropwise addition over 15 minutes of a solution of fuming 24N nitric acid (7.42 ml, 178 mmol) in methylene chloride (15 ml). After completion of the addition, the solution was allowed to warm up and stirred at ambient temperature for 2 hours. The volatiles were removed under vacuum and the residue was dissolved in methylene chloride (50 ml). The solution was cooled to 0-5° C. and ether was added. The precipitate was collected by filtration, and dried under vacuum at 50° C. The solid was dissolved in methylene chloride (500 ml) and 3M hydrogen chloride in ether (30 ml) was added followed by ether (500 ml). The solid was collected by filtration and dried under vacuum at 50° C. to give ethyl 3-methoxy-4-(1-methylpiperidin-4-ylmethoxy)-6-nitrobenzoate (28.4 g, 82%).

Workup

  1. additionfollowed by the dropwise addition over 15 minutes of a solution
  2. additionAfter completion of the addition
  3. temperatureto warm up
  4. customThe volatiles were removed under vacuum
  5. dissolutionthe residue was dissolved in methylene chloride (50 ml)
  6. temperatureThe solution was cooled to 0-5° C.
  7. additionether was added
  8. filtrationThe precipitate was collected by filtration
  9. customdried under vacuum at 50° C
  10. dissolutionThe solid was dissolved in methylene chloride (500 ml)
  11. addition3M hydrogen chloride in ether (30 ml) was added
  12. filtrationThe solid was collected by filtration
  13. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-edc971168b5f45c3a078ffce6b629139
Source dataset
uspto-grants-2014_02
Patent number
US08642608B2

Reaction notes

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