Stearic Acid → 1-[5-(2-Pyridinyl)-2-oxazolyl]-1-octadecanone

Temperature

0 °C

(182) A solution of 2-(oxazol-5-yl)pyridine (113 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, 1.54 mmol, 3.1 mL) was added at −75° C., and stirred for 45 min at 0° C. Cul (1.0 equiv, 0.77 mmol, 147 mg) was added, and the solution was stirred for 10 min at 0° C. A separate flask was charged with stearic acid (2 equiv, 1.54 mmol, 440 mg) in anhydrous CH2Cl2 (4.2 mL), and to this solution cooled to 0° C. under N2 was added oxalyl chloride (5 equiv, 7.7 mmol, 0.98 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 stearoyl 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)octadecan-1-one (182) (97 mg, 0.24 mmol, 31% yield) as a white powder: mp 86-87° C.; 1H NMR (CDCl3, 250 MHz) d 8.66 (br d, J=5.4 Hz, 1H), 7.89-7.76 (m, 3H), 7.34-7.27 (m, 1H), 3.10 (t, J=7.7 Hz, 2H), 1.82-1.74 (m, 2H), 1.44-1.19 (m, 28H), 0.87 (br t, J=6.6 Hz, 3H); 13C NMR (CDCl3, 62.5 MHz) d 188.6, 157.4, 153.2, 150.1 (2C), 137.1, 126.8, 124.1, 120.3, 39.2, 31.9, 29.7 (5C), 29.6 (2C), 29.6, 29.4, 29.3 (2C), 29.2, 24.0, 22.7, 14.1; IR (KBr) umax 2942, 2871, 1701, 1601, 1429, 1376 cm−1; MALDI-FTMS (DHB) m/z 413.3170 (C26H40N2O2+H+ requires 713.3162).

1. stirringstirred for 45 min at 0° C
2. additionCul (1.0 equiv, 0.77 mmol, 147 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 stearoyl 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-0505191777f8433cb66616f08fd331a5

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07662971B2