Chloroacetone → 5-Methyl-3-(2-oxopropyl)-1,3,4-oxadiazol-2(3H)-one

To a solution of 5-methyl-3H-1,3,4-oxadiazol-2-one (5.509 g, 55.0 mmol) in MeOH (40 mL) is added 25 wt % NaOMe solution in methanol (12.7 mL, 58.8 mmol). The mixture is stirred at rt for 15 min and then concentrated in vacuo. The residue is added to a solution of tetrabutylammonium bromide (0.358 g, 1.08 mmol) and chloro-acetone (4.6 ml, 54.9 mmol) in CHCl3 (33 mL), and the mixture is heated to reflux for 5 h under N2. The mixture is cooled to rt and stirred overnight. The resulting slurry is filtered, and the filtrate is concentrated in vacuo. The residue is purified on a pad of silica gel, eluting with 2:1:1/heptane:EtOAc:DCM to afford 5-methyl-3-(2-oxo-propyl)-3H-1,3,4-oxadiazol-2-one (7.32 g, 86%) as a crystalline solid. MS: 157 (M+H); 1H NMR (300 MHz, CDCl3) δ 4.46 (s, 2H), 2.27 (s, 3H), 2.21 (s, 3H).

1. concentrationconcentrated in vacuo
2. temperaturethe mixture is heated
3. temperatureto reflux for 5 h under N2
4. temperatureThe mixture is cooled to rt
5. stirringstirred overnight
6. filtrationThe resulting slurry is filtered
7. concentrationthe filtrate is concentrated in vacuo
8. customThe residue is purified on a pad of silica gel
9. washeluting with 2:1:1/heptane

ORD record

ord-22f2223f7287441fbf70f9f9732759b8

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258130B2