Ethyl ethoxyacetate → Ethoxymethyl 5-methyl-1,3,4-oxadiazol-2-yl ketone

Temperature

-40 °C

To a stirred solution of the 2-methyl-1,3,4-oxadiazole (5.0 g, 59.5 mmol) in THF (100 mL) was added dropwise n-BuLi (23.79 mL, 59.5 mmol) in toluene under N2 at −78° C. After 1 h, ethyl ethoxyacetate (10.22 g, 77 mmol) was added. The reaction mixture was then allowed to warm to −40° C. and stirred for 2 h. The reaction mixture was then quenched with 65 mL of LON HCl and extracted with EtOAc. The organic layer was washed with water and then brine, dried over anhydrous Na2SO4, and concentrated. The resulting residue was purified on a flash chromatography column (Biotage™-40M) using a gradient of 0-100% of n-hexane/Et2O to give the desired product. 1H NMR (500 MHz, CD3OD): δ 1.27 (t, 3H), 2.64 (s, 3H), 3.69 (q, 2H), 4.88 (s, 2H).

1. customThe reaction mixture was then quenched with 65 mL of LON HCl
2. extractionextracted with EtOAc
3. washThe organic layer was washed with water
4. dry with materialbrine, dried over anhydrous Na2SO4
5. concentrationconcentrated
6. customThe resulting residue was purified on a flash chromatography column (Biotage™-40M)

ORD record

ord-6fa059c989d04a55b66333cae6dca4f2

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754099B2