Cl[C:2]1[C:7]([C:8]2([OH:12])[CH2:11][O:10][CH2:9]2)=[CH:6][N:5]=[C:4]([C:13]#[N:14])[CH:3]=1.[F:15][C:16]([F:20])([F:19])[CH2:17][OH:18].CC(C)([O-])C.[K+]>CN(C=O)C>[OH:12][C:8]1([C:7]2[C:2]([O:18][CH2:17][C:16]([F:20])([F:19])[F:15])=[CH:3][C:4]([C:13]#[N:14])=[N:5][CH:6]=2)[CH2:11][O:10][CH2:9]1To a solution of 4-chloro-5-(3-hydroxyoxetan-3-yl)pyridine-2-carbonitrile (example 123b, 1 g, 4.75 mmol) in dry DMF (20 ml) under an argon atmosphere cooled down to 0° C. was added 2,2,2-trifluoroethanol (570 mg, 412 μl, 5.7 mmol) followed by addition of potassium tert-butoxide (639 mg, 5.7 mmol). The reaction was stirred at 0° C. for 10 minutes and then stirred at 80° C. for 2 hours. DMF was removed in vacuo and the residue was dissolved in ethylacetate. The organic phase was extracted with a 2M aqueous solution of sodium carbonate. The organic phase was collected and the aqueous phase back-extracted with ethylacetate. The combined organic phases were dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (1.2 gr, 92%); MS (ESI, m/z): 275.4 (M+H+).
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