Acetic Anhydride → 3,5-Dioxohexanoic acid

Nervonic acid (3.0 g, 8.2 mmol) was dissolved in anhydrous THF (100 mL) at 5° C. followed by NHS (1.88 g, 16.3 mmol) and DCC (3.38 g, 16.3 mmol). The mixture was heated to reflux for 2 h. Phytosphingosine dissolved in THF and pyridine was added to the reaction mixture and refluxed for 12 h. Acetic anhydride (9 mL) was added followed by triethylamine (9 mL), DMAP (300 mg), and the mixture was stirred for 2 h. The solvent was removed in vacuo. Triacetate 7 (3.4 g, 48.6% yield) was isolated by chromatography (SiO2, EtOAc:Hexane 1:8). Sodium metal (230 mg, 10 mmol) was added to MeOH (100 mL). Triacetate 7 (3.4 g, 4.4 mmol) was added, and the mixture was stirred for 1 h then centrifuged (3000 rpm, 5 m) to give a white solid. The supernatant was removed, and the solid rinsed with fresh MeOH (80 mL) to remove any remaining base. After removal of the supernatant, the crude white solid (2.1 g, 71%) was dried under vacuo. NMR (1H, CDCl3) d 6.14 (d, J=9.5, 1 H), 5.34 (m, 2 H), 5.12 (dd, J=3, 8.5 Hz, 1 H), 4.93 (m, 1 H), 4.50 (m, 1 H), 4.29 (dd, J=5, 11.5 Hz, 1 H), 4.0 (dd, J=3.0, 11.5 Hz, 1 H), 2.21 (t, J=7.5 Hz, 2 H), 2.08 (s, 3 H), 2.05-1.99 (m, 10 H), 1.66-1.60 (m, 4 H), 1.33-1.22 (m, 56 H), 0.89 (t, J=7.0 Hz, 6 H); NMR (13C, CDCl3) d 178.25, 173.19, 171.31, 170.99, 170.20, 129.99, 73.15, 71.92, 63.05, 60.52, 47.50, 36.81, 34.11, 32.05, 29.91, 29.83, 29.80, 29.74, 29.67, 29.51, 29.45, 29.39, 29.26, 28.10, 27.33, 25.80, 25.68, 24.92, 22.82, 21.13, 20.88, 20.84, 14.30, 14.24. HRFAB-MS (thioglycerol+Na+ matrix) m/e ([M+Na]+) 814.6526, calcd 814.6537.

1. temperatureThe mixture was heated
2. temperatureto reflux for 2 h
3. temperaturerefluxed for 12 h
4. customThe solvent was removed in vacuo

ORD record

ord-36a564cf7eca4470924407c4cc5b6e4d

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08227581B2