Hydrochloric Acid → 2-Methyl-2-phenyl-propionic acid, dimethylamide

HRID 1857849Notes

Reaction equation

HRID 1857849 reaction equation
[CH3:1][C:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH3:6])[C:3](O)=[O:4].S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:24][NH:25][CH3:26].Cl>C1(C)C=CC=CC=1.O.C(OC)(C)(C)C>[CH3:24][N:25]([CH3:26])[C:3](=[O:4])[C:2]([CH3:6])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:1]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10473Dimethylamine, hydrochlorideHCID 11430Potassium CarbonateHCID 132222-Phenylisobutyric acidHCID 24386Thionyl Chloride2×

Product 1

HCID 540072552-Methyl-2-phenyl-propionic acid, dimethylamideYield 88%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Dissolve 2-methyl-2-phenyl-propionic acid (15.0 g, 91.2 mmol) in toluene (80 mL) and add, by dropwise addition over 5 minutes, thionyl chloride (15 mL, 206 mmol). Stir at room temperature overnight, add additional thionyl chloride (3 mL, 41.1 mmol) and heat to reflux for 1 hour. Remove excess thionyl chloride by azeotropic distillation with toluene (40 mL). Add toluene (20 mL) to the reaction mixture along with a solution of potassium carbonate (28.0 g, 203 mmol) in water (40 mL). Add, by dropwise addition, a 40% aqueous solution of dimethylamine hydrochloride (20 mL, 0.18 mol) without cooling and stir for 2 hours. Add tert-butylmethyl ether (75 mL) following by slow addition of aqueous HCl (2N, 75 mL) with vigorous stirring. Separate the organic layer and wash with aqueous HCl (2N, 75 mL), saturated sodium hydrogen carbonate (25 mL) and brine (50 mL). Dry the organic layer over (Na2SO4), filter, evaporate the filtrate in vacuo and purify by crystallization to give 2-methyl-2-phenyl-propionic acid, dimethylamide (15.35 g, 88%) as a white solid; mp 57-59° C.

Workup

  1. additionadd, by dropwise addition over 5 minutes
  2. temperatureheat
  3. temperatureto reflux for 1 hour
  4. distillationRemove excess thionyl chloride by azeotropic distillation with toluene (40 mL)
  5. additionAdd, by dropwise addition
  6. stirringstir for 2 hours
  7. customSeparate the organic layer
  8. washwash with aqueous HCl (2N, 75 mL), saturated sodium hydrogen carbonate (25 mL) and brine (50 mL)
  9. dry with materialDry the organic layer over (Na2SO4)
  10. filtrationfilter
  11. customevaporate the filtrate in vacuo
  12. custompurify by crystallization

Sources & evidence

ORD record
ord-48b74901d43e4fd491c3ec0a9975edd8
Source dataset
uspto-grants-2000_11
Patent number
US06147216

Reaction notes

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