Ethyl formate → 2-Cyclopropyl-1,3-oxazole-4-carbonitrile

Temperature

-10 °C

To a solution of N-cyanomethyl-cyclopropanecarboximidic acid ethyl ester (4.54 g, 14.9 mmol) in THF (10 mL) at −10° C. were added potassium tert-butoxide (1.67 g, 14.9 mmol) and ethyl formate (1.2 mL, 14.9 mmol) successively. After being stirred at −10° C. for 3 h, the reaction mixture was left in the refrigerator overnight and then diluted with ether. The precipitated brown solid was filtered and dried under vacuum. The vacuum-dried solid was added to boiling acetic acid (45 mL) and refluxed for 2 min. The reaction mixture was cooled to room temperature, diluted with water, and adjusted to pH 7 by adding 1 N sodium hydroxide. The reaction mixture was extracted with ether (2×1 L). The combined organic fractions were dried (MgSO4), filtered, and concentrated. The crude brownish solid was chromatographed (silica gel, 0-50% EtOAc in Hexane, detection KMnO4 spray, Rf=0.3 in 10% EtOAc/Hexane) to give 2-cyclopropyl-oxazole-4-carbonitrile as a colorless liquid (463 mg).

1. waitthe reaction mixture was left in the refrigerator overnight
2. filtrationThe precipitated brown solid was filtered
3. customdried under vacuum
4. additionThe vacuum-dried solid was added
5. temperaturerefluxed for 2 min
6. temperatureThe reaction mixture was cooled to room temperature
7. additiondiluted with water
8. additionby adding 1 N sodium hydroxide
9. extractionThe reaction mixture was extracted with ether (2×1 L)
10. dry with materialThe combined organic fractions were dried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude brownish solid was chromatographed (silica gel, 0-50% EtOAc in Hexane, detection KMnO4 spray, Rf=0.3 in 10% EtOAc/Hexane)

ORD record

ord-f0b5cd872ed746efb838f1a648dc7585

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08552205B2