Ammonium Hydroxide → 6-Cyclopropyl-2,4-dimethyl-nicotinic acid ethyl ester

HRID 1711154Notes

Reaction equation

HRID 1711154 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[CH:5]=[CH:4][N:3]=1.[CH:14]1(C(O)=O)[CH2:16][CH2:15]1.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].[NH4+].[OH-]>OS(O)(=O)=O.O.[N+]([O-])([O-])=O.[Ag+]>[CH2:11]([O:10][C:8](=[O:9])[C:7]1[C:6]([CH3:13])=[CH:5][C:4]([CH:14]2[CH2:16][CH2:15]2)=[N:3][C:2]=1[CH3:1])[CH3:12]

Participants

8

Reactant 4

HCID 14923Ammonium HydroxideHCID 15655Cyclopropanecarboxylic acidHCID 62648Ammonium PersulfateHCID 736245Ethyl 2,4-dimethylnicotinate

Product 1

HCID 687768336-Cyclopropyl-2,4-dimethyl-nicotinic acid ethyl esterYield 18%

Reagents, catalysts & solvents 3

HCID 24470Silver NitrateCatalystHCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Procedure

To a solution of ethyl 2,4-dimethylpyridine-3-carboxylate (0.59 g, 3.29 mmol) and cyclopropane carboxylic acid (1.2 ml (15.1 mmol) in 10% aqueous H2SO4 (3 ml) was added AgNO3 (154 mg, 0.91 mmol) followed by a solution of ammonium persulfate (1:541 g, 6.75 mmol) in water (6 ml) and the mixture stirred at room temperature overnight. The reaction was neutralized to pH 10 with saturated aqueous NH4OH (5 ml) and extracted with EtOAc (3×20 ml). The combined organic extracts were dried (Na2SO4), concentrated and purified by column chromatography on silica gel (Hexanes/EtOAc, 96:4 then 1:1 then 0:100) to afford desired 6-cyclopropyl-2,4-dimethyl-nicotinic acid ethyl ester (133 mg, 18%) as a clear oil along with recovered starting ethyl 2,4-dimethylpyridine-3-carboxylate (0.31 g). 1H NMR (CDCl3) δ 0.93-0.97 (m, 4H), 1.38 (t, 3H, J=6 Hz), 1.92-2.02 (m, 1H), 2.28 (s, 3H), 2.47 (s, 3H), 4.39 (q, 2H, J=6 Hz), 6.73 (s, 1H).

Workup

  1. extractionextracted with EtOAc (3×20 ml)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated
  4. custompurified by column chromatography on silica gel (Hexanes/EtOAc, 96:4

Sources & evidence

ORD record
ord-dd77f1aa9d69488f91bcb34894fc3b18
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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