Phosphorus oxychloride → HCID 59334802, compound

Participants

Reaction Conditions

Reaction Steps

3′-Fluoro-4-hydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonitrile 19 (100 g, 450.2 mMol) was dissolved in dry pyridine (1,000 mL) and cooled to 0° C. under nitrogen. Phosphorus oxychloride (85 mL, 940 mMol) was added dropwise ensuring the temperature did not rise above 10° C. during the addition, and the resulting mixture stirred at 0° C. overnight using a lagged cooling bath. The mixture was cautiously poured into ice-water (3,000 mL) with stirring, and the pH adjusted to 6.0 using potassium phosphate buffer. The mixture was extracted with ethyl acetate (3×2,000 mL), dried (MgSO4) and the solvent evaporated to dryness in vacuo to leave orange oil. Flash chromatography of the residue eluting with hexanes:ethyl acetate (10:1) gave the title compound 20 (65 g, 72%) as a white solid m.p.=76-77° C. δH {400 MHz, CDCl3} 8.01 (1H, d, J=5 Hz), 7.27 (1H, dd, J=20, 8 Hz), 6.79 (1H, m), 6.71 (1H, m), 4.16 (2H, dd, J=12, 3 Hz), 3.65 (2H, t, J=6 Hz), 2.50 (2H, m).

Provenance & Evidence