Nitric Acid → 6-Methoxycarbonylmethoxy-5-nitro-nicotinic acid ethyl ester

HRID 2386738Notes

Reaction equation

HRID 2386738 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8](Cl)=[N:7][CH:6]=1)[CH3:2].O[C:17]1C=CC(C(O)=O)=CN=1.[N+]([O-])(O)=O.P(Cl)(Cl)(Cl)(Cl)Cl.O=P(Cl)(Cl)Cl.C[CH:42]([OH:46])[C:43]([O-:45])=[O:44].[H-].[Na+]>O1CCOCC1.O.CCO>[CH2:1]([O:3][C:4](=[O:15])[C:5]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:46][CH2:42][C:43]([O:45][CH3:17])=[O:44])=[N:7][CH:6]=1)[CH3:2]

Participants

11

Reactant 7

HCID 944Nitric AcidHCID 24758Sodium hydrideHCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 91435LactateHCID 3784053Ethyl 6-chloro-5-nitronicotinateHCID 178418479HCID 178418479, compound

Product 1

HCID 675470856-Methoxycarbonylmethoxy-5-nitro-nicotinic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-chloro-5-nitro-nicotinic acid ethyl ester (10.5 g, prepared from 6-hydroxy-nicotinic acid with a) fuming nitric acid, b) PCl5, POCl3, c) EtOH, see WO2005012288) in dioxan (100 ml) was added methylglycolate (4.92 g). Sodium hydride (55% dispersion in mineral oil, 2.19 g) was added portion wise at 0° C. The mixture was stirred at room temperature for 24 h. Water was added and the mixture was extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>7:3) to give the title compound (3.026 g) as yellow oil. MS (m/e)=285.2 [M+H+].

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:0=>7:3)

Sources & evidence

ORD record
ord-fc8596174a8146999afb95990bb53087
Source dataset
uspto-grants-2012_09
Patent number
US08268820B2

Reaction notes

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