Acetic Acid → Ethyl 2,4-dimethyl-1,3-oxazole-5-carboxylate

Prepared as in J. Heterocyclic Chem. 1998, 35, 859. A solution of chloroacetoacetate (20 g, 121 mmol) and acetamide (14.4 g, 240 mmol) in glacial acetic acid (40 mL) was heated to reflux for 72 h. The mixture was cooled to rt and concentrated under vacuum. The resulting material was cooled in an ice bath and made basic (pH 9-10) with 6 N NaOH solution. The aqueous solution was extracted with Et2O (3×100 mL). The combined Et2O layers were dried (Na2SO4), filtered, and concentrated to afford a light brown oil. The crude material was purified by silica gel chromatography, eluting with a gradient of 20 % EtOAc/hexanes to 25 % EtOAc/hexanes to provide the ester (1.8 g, 9 %) as a pale yellow solid. 1H NMR 300 MHz (CDCl3): δ=4.37 (q, J=7.1 Hz, 2 H), 2.49 (s, 3H), 2.43 (s, 3H), 1.38 (t, J=7.1 Hz, 3H). MS (ESI-POS): [M+H]+=191.

1. customPrepared as in J
2. temperatureto reflux for 72 h
3. concentrationconcentrated under vacuum
4. temperatureThe resulting material was cooled in an ice bath
5. extractionThe aqueous solution was extracted with Et2O (3×100 mL)
6. dry with materialThe combined Et2O layers were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a light brown oil
10. customThe crude material was purified by silica gel chromatography
11. washeluting with a gradient of 20 % EtOAc/hexanes to 25 % EtOAc/hexanes

ORD record

ord-f09c1606d46744f9b64775c4db299116

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07696210B2