Cyclopropanemethanol → 6-(Cyclopropylmethoxy)-5-(3-fluorooxetan-3-yl)pyridine-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

6-Chloro-5-(3-fluorooxetan-3-yl)pyridine-2-carboxylic acid (Example 134 e, 44 mg, 190 μmol) and cyclopropylmethanol (CAN 2516-33-8, 17.8 mg, 20.0 μL, 247 μmol) were dissolved in DMF (1.32 mL). A solution of sodium 2-methylpropan-2-olate (42.0 mg, 437 μmol) in THF (800 μL) was added and the mixture was heated to 50° C. for 3 h and for additional 3 h to 70° C. After cooling to ambient temperature, the reaction mixture was poured onto ice/0.1 N HCl (25 mL) and extracted with EtOAc (2×25 mL). The combined extracts were washed with ice/brine (20 mL), dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by thin layer chromatography (2 mm SiO2, dichloromethane/MeOH 19:1, elution with EtOAc) to give the title compound (11 mg, 22 mg) as colorless oil, MS (ESI) m/e=268.2 [MH+].

Provenance & Evidence