3-Oxetanone → 6-Cyclopropylmethoxy-5-(3-hydroxy-oxetan-3-yl)-pyridine-2-carboxylic acid

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Reaction Steps

Under a nitrogen atmosphere, n-BuLi (3.23 mL, 5.6 mmol) was added dropwise to a solution of 5-bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 9 d, 1.1 g, 4.0 mmol) in THF (50 mL) at −78° C. and stirred for 1 h at this temperature. Then a solution of oxetan-3-one (CAN 6704-31-0, 0.73 g, 10 mmol) in THF (5 mL) was added at −78° C. The reaction mixture was stirred for 1 h at room temperature and quenched with aq. NH4Cl solution. The pH was adjusted to 2 with conc. HCl. The mixture was extracted with ethyl acetate (3×50 mL), the organic layers were combined, washed with brine (2×50 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by chromatography over silica gel using petroleum ether/ethyl acetate=1/1 to give the title compound (0.13 g, 30.8%) as a yellow solid; MS (EI): m/e=266.1 [M+H]+.

Provenance & Evidence