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

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Reaction Steps

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)−.

Provenance & Evidence