3,4-Dimethoxybenzeneacetonitrile → 3,4-Dimethoxybenzyl 3-pyridyl ketone

HRID 464319Notes

Reaction equation

HRID 464319 reaction equation
[C:1]([O:9]CC)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][C:22]=1[O:23][CH3:24])[CH2:17]C#N.CC[O-].[Na+].[Na]>O.C(O)C>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:1]([CH2:17][C:16]2[CH:20]=[CH:21][C:22]([O:23][CH3:24])=[C:14]([O:13][CH3:12])[CH:15]=2)=[O:9])[CH:3]=1

Participants

7

Reactant 4

HCID 667273,4-DimethoxybenzeneacetonitrileHCID 69188Ethyl NicotinateHCID 2723922Sodium ethoxideHCID 5360545Sodium

Product 1

HCID 133198913,4-Dimethoxybenzyl 3-pyridyl ketone

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 45.4 g of ethyl nicotinate and 35.4 g of 3,4-dimethoxybenzyl cyanide is added dropwise to a boiling solution of sodium ethylate prepared from 6 g of sodium and 100 ml of ethanol. The mixture is kept at reflux for 5 hours and, after cooling, is poured into 1 liter of water. The excess nicotinic ester is removed with toluene, and the aqueous solution is neutralized with glacial acetic acid, 50.7 g of α-cyano-3,4-dimethoxybenzyl 3-pyridyl ketone separating out as crystals (melting point 149°-152° C.). This cyanoketone (31.0 g) is hydrolyzed in 6N hydrochloric acid at 80°-90° C. The hydrochloride of the 3,4-dimethoxybenzyl 3-pyridyl ketone crystallizes from ethanol with melting point 188°-191° C. and the free base has a melting point of 60°-64° C. The compound is converted into the oxime without further purification.

Workup

  1. temperatureat reflux for 5 hours
  2. temperatureafter cooling
  3. customThe excess nicotinic ester is removed with toluene
  4. customis hydrolyzed in 6N hydrochloric acid at 80°-90° C
  5. customThe hydrochloride of the 3,4-dimethoxybenzyl 3-pyridyl ketone crystallizes from ethanol with melting point 188°-191° C.
  6. customThe compound is converted into the oxime without further purification

Sources & evidence

ORD record
ord-d8ec3d2c17f24be7ac7404389ec78424
Source dataset
uspto-grants-1985_10
Patent number
US04547508

Reaction notes

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