Nonanoic Acid → HCID 11426192, compound

Temperature

0 °C

(188) A solution of 2-(oxazol-5-yl)pyridine (117 mg, 0.80 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, 0.88 mmol, 0.35 mL), and stirred for 20 min. ZnCl2 (0.5 M in THF, 2.0 equiv, 1.60 mmol, 3.2 mL) was added at −75° C., and stirred for 45 min at 0° C. Cul (1.0 equiv, 0.80 mmol, 152 mg) was added, and the solution was stirred for 10 min at 0° C. A separate flask was charged with nonanoic acid (2 equiv, 1.60 mmol, 253 mg, 0.28 mL) in anhydrous CH2Cl2 (4.2 mL), and to this solution cooled to 0° C. under N2 was added oxalyl chloride (5 equiv, 8.0 mmol, 1.02 g, 0.70 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 nonanoyl 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)nonan-1-one (188) (94 mg, 0.33 mmol, 41% yield) as a light brown powder: mp 56-57° C.; 1H NMR (CDCl3, 250 MHz) d 8.61 (br d, J=4.4 Hz, 1H), 7.84-7.71 (m, 3H), 7.29-7.22 (m, 1H), 3.05 (t, J=7.3 Hz, 2H), 1.79-1.66 (m, 2H), 1.42-1.16 (m, 10H), 0.88-0.77 (m, 3H); 13C NMR (CDCl3, 62.5 MHz) d 188.4, 157.3, 153.1, 150.0, 146.2, 137.0, 126.8, 124.0, 120.3, 39.0, 31.7, 29.2, 29.0, 24.0, 23.9, 22.5, 14.0; IR (KBr) umax 2922, 2856, 1705, 1697, 1600, 1420, 1381 cm−1; MALDI-FTMS (DHB) m/z 287.1744 (C17H22N2O2+H+ requires 287.1754).

1. stirringstirred for 45 min at 0° C
2. additionCul (1.0 equiv, 0.80 mmol, 152 mg) was added
3. stirringthe solution was stirred for 10 min at 0° C
4. stirringAfter stirring at rt for 2 h
5. concentrationthe solution was concentrated under reduced pressure
6. dissolutiondissolved in anhydrous THF (1.5 mL)
7. additionThe solution of nonanoyl chloride was added
8. stirringthe solution was stirred for 1 h at 0° C
9. additionThe reaction was diluted with EtOAc (10 mL)
10. washwashed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL)
11. dry with materialThe organic layer was dried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure

ORD record

ord-7416f17e4b0b491ca6f3bf2108852f44

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662971B2