Hydrochloric Acid → N-Methoxy-N-methyl-2-phenyl-isobutyramide

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 (400 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 solution of N,O-dimethylhydroxylamine hydrochloride (8.9 g, 91.2 mmol) in water (20 mL) 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 hydrogen carbonate (25 mL) and brine (50 mL). Dry the organic layer over (Na2SO4), filter, evaporate the filtrate in vacuo and purify by vacuum distillation to give 2-methyl-2-phenyl-propionic acid, N-methoxy-N-methylamide (18.0 g, 95%); bp 91-103° C/5 mm Hg.

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 (400 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 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. distillationpurify by vacuum distillation

ORD record

ord-4348db74ab664981a349676cf45eeb23

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06777555B2