Hydrochloric Acid → 5-Cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinic acid

In a 25 mL round-bottomed flask, the above prepared 5-cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid methyl ester (830 mg, 3.02 mmol, Eq: 1.00) was combined with tetrahydrofuran (7 ml) and water (3.5 ml) to give a light yellow bi-phasic system. Lithium hydroxide (86.7 mg, 3.62 mmol, Eq: 1.2) was added and the reaction mixture was stirred vigorously at rt. TLC after ˜20 h showed the reaction to be incomplete with some remaining starting material. More lithium hydroxide (43.3 mg, 1.81 mmol, Eq: 0.6) was added and the reaction mixture was stirred at 40° C. TLC after 1 additional h indicated that the reaction was complete. Work up: 10 ml H2O and 7 ml 1N HCl were added and the reaction mixture was extracted with AcOEt (2×50 ml). The organic layers were washed with H2O/NaCl sol, combined, dried over Na2SO4 and concentrated in vacuo. The residue was triturated with heptane to afford 766 mg of the title compound as white powder; MS (EI) 260.0 (M−H)−.

1. customto give a light yellow bi-phasic system
2. customthe reaction
3. stirringthe reaction mixture was stirred at 40° C
4. extractionthe reaction mixture was extracted with AcOEt (2×50 ml)
5. washThe organic layers were washed with H2O/NaCl
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customThe residue was triturated with heptane

ORD-Eintrag

ord-afc2aa166f06495fb8806cbe091d41eb

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08648099B2