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

HRID 1836771Notes

Reaction equation

HRID 1836771 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 30 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 (400 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 30 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-9b7ac9e0eb28426287c3a150f9539cc0
Source dataset
uspto-grants-2004_08
Patent number
US06777555B2

Reaction notes

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