Reaction Steps
(190) A solution of 2-(oxazol-5-yl)pyridine (112 mg, 0.77 mmol) in anhydrous THF (5 mL) cooled to −75° C. under N2 was treated with n-BuLi (2.5 M in hexanes, 1.1 equiv, 0.85 mmol, 0.34 mL), and stirred for 20 min. ZnCl2 (0.5 M in THF, 2.0 equiv, 1.58 mmol, 3.1 mL) was added at −75° C., and stirred for 45 min at 0° C. Cul (1.0 equiv, 0.77 mmol, 146 mg) was added, and the solution was stirred for 10 min at 0° C. A separate flask was charged with heptanoic acid (2 equiv, 1.55 mmol, 202 mg, 0.22 mL) in anhydrous CH2Cl2 (4.2 mL), and to this solution cooled to 0° C. under N2 was added oxalyl chloride (5 equiv, 7.8 mmol, 0.99 g, 0.68 mL). After stirring at rt for 2 h, the solution was concentrated under reduced pressure and dissolved in anhydrous THF (1.5 mL). The solution of heptanoyl chloride was added and the solution was stirred for 1 h at 0° C. The reaction was diluted with EtOAc (10 mL), and washed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. Flash chromatography (SiO2, 2.5 cm×17.5 cm, 20% EtOAc-hexanes) afforded 1-(5-(pyridin-2-yl)oxazol-2-yl)heptan-1-one (190) (97 mg, 0.38 mmol, 49% yield) as a light brown powder mp 52° C.; 1H NMR (CDCl3, 250 MHz) d 8.63 (br d, J=4.8 Hz, 1H), 7.85-7.74 (m, 3H), 7.31-7.25 (m, 1H), 3.08 (t, J=7.7 Hz, 2H), 1.78-1.69 (m, 2H), 1.44-1.22 (m, 6H), 0.68 (t, J=6.6 Hz, 3H); 13C NMR (CDCl3, 62.5 MHz) d 188.5, 157.3, 153.2, 150.0, 146.3, 137.0, 126.8, 124.1, 120.3, 39.1, 31.4, 28.8, 23.9, 22.4, 14.0; IR (KBr) umax 2933, 2847, 1698, 1604, 1430, 1387 cm−1; MALDI-FTMS (DHB) m/z 259.1436 (C15H18N2O2+H+ requires 259.1441).
