Toluene → Methyl 2-cyclopropyl-6-(trifluoromethyl)nicotinate

To a stirring solution of (Z)-4-amino-1,1,1-trifluorobut-3-en-2-one (3 g, 21.58 mmol) and methyl 3-cyclopropyl-3-oxopropanoate (3.7 g, 26.03 mmol) in toluene (20 mL) at room temperature under argon was added TFA (2.96 g, 25.92 mmol). The reaction mixture was stirred at reflux for 10 h. The reaction mixture was then cooled to room temperature and concentrated under vacuum to obtain a gum. EtOAc (50 mL) and 15% aqueous sodium carbonate solution (50 mL) were added, and the resulting mixture was stirred at room temperature for 10 min. The organic layer was separated, washed with brine, dried (MgSO4), filtered and concentrated to obtain crude product as a yellow oil. This crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes) to isolate 1 g of the title compound as a pale yellow oil. HPLC/MS: retention time=3.618 min, [M+H]+=246.

1. temperatureat reflux for 10 h
2. concentrationconcentrated under vacuum
3. customto obtain a gum
4. stirringthe resulting mixture was stirred at room temperature for 10 min
5. customThe organic layer was separated
6. washwashed with brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto obtain crude product as a yellow oil
11. customThis crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes)

ORD record

ord-b9b6cd5757994300828ecead8178efc0

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572808B2