Ammonia → 2-bromo-N-(2,6-dimethyl-4-trifluoromethyl-3-pyridyl)acetamide

3-Amino-2,6-dimethyl-4-trifluoromethylpyridine dihydrochloride (15.60 g, 59.30 mmol) was dissolved in methanol (100 mL). In an ice bath, saturated ammonia in methanol (300 mL) was added to the solution, followed by sufficiently mixing to form a uniform mixture. The reaction mixture was extracted with chloroform-water, and the organic layer was washed with saturated brine, followed by drying over sodium sulfate anhydrate and concentration under reduced pressure. The thus-obtained residue was suspended in dichloromethane (200 mL), and N,N-dimethylaniline (10.80 g, 89.12 mmol) was added thereto. Under stirring on an ice bath, bromoacetyl bromide (15.52 g, 76.90 mmol) in dichloromethane (40 mL) was added dropwise to the mixture, followed by stirring for 2 hours at room temperature. The reaction mixture was concentrated under reduced pressure. The thus-obtained residue was purified through silica gel column chromatography (eluent: n-hexane/acetone=10/1→4/1→3/1), followed by recrystallization from ethyl acetate-hexane, to thereby yield 2-bromo-N-(2,6-dimethyl-4-trifluoromethylpyridin-3-yl)acetamide as colorless needles (17.68 g, 96%).

1. additionby sufficiently mixing
2. customto form a uniform mixture
3. extractionThe reaction mixture was extracted with chloroform-water
4. washthe organic layer was washed with saturated brine
5. dry with materialby drying over sodium sulfate anhydrate and concentration under reduced pressure
6. stirringby stirring for 2 hours at room temperature
7. concentrationThe reaction mixture was concentrated under reduced pressure
8. customThe thus-obtained residue was purified through silica gel column chromatography (eluent: n-hexane/acetone=10/1→4/1→3/1)
9. customfollowed by recrystallization from ethyl acetate-hexane

ORD record

ord-3ca93d67756841ff9751755b994317fc

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07459552B2