Hydrochloric Acid → 2-Chloro-3-p-tolyl-propionic acid methyl ester

HRID 643233Notes

Reaction equation

HRID 643233 reaction equation
N([O-])=O.[Na+].CC(C)=O.C(=O)=O.N[C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1.[ClH:20].[C:21]([O:25][CH3:26])(=[O:24])[CH:22]=[CH2:23]>O.[Cu]I.CC(C)=O>[CH3:26][O:25][C:21](=[O:24])[CH:22]([Cl:20])[CH2:23][C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 7813p-ToluidineHCID 18522661Acetone cardiceHCID 23668193Sodium Nitrite

Product 1

HCID 143978892-Chloro-3-p-tolyl-propionic acid methyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A solution of sodium nitrite (16.5 g, 0.24 mol) in 50 ml of water is slowly added to a mechanically stirred, acetone-dry ice cooled suspension of p-toluidine (23.5 g, 0.22 mol), 250 ml of acetone and 50 ml of concentrated hydrochloric acid in such manner, that the reaction temperature does not exceed +5° C. The mixture is stirred for 1 hour at +5° C. and then 100 ml of methyl acrylate are added. The suspension is then warmed to +30° C. Copper(I) iodide (1 g, 5 mmol) is added portionwise over 30 minutes such that the temperature of the reaction mixture does not exceed +35° C., and the stirring is continued for an additional 30 minutes at this temperature. The solvent is evaporated under reduced pressure, the residue is diluted with water and extracted with dichloromethane. The combined organic layer is washed with water, dried over magnesium sulfate and evaporated. The residue is purified by chromatography on silica gel (ethyl acetate/hexane 9:1) to obtain 2-chloro-3-p-tolyl-propionic acid methyl ester.

Workup

  1. customdoes not exceed +5° C
  2. stirringThe mixture is stirred for 1 hour at +5° C.
  3. temperatureThe suspension is then warmed to +30° C
  4. customdoes not exceed +35° C.
  5. customThe solvent is evaporated under reduced pressure
  6. additionthe residue is diluted with water
  7. extractionextracted with dichloromethane
  8. washThe combined organic layer is washed with water
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. customThe residue is purified by chromatography on silica gel (ethyl acetate/hexane 9:1)

Sources & evidence

ORD record
ord-d446e8df79824abea84fb1b52937a567
Source dataset
uspto-grants-2010_04
Patent number
US07700522B2

Reaction notes

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