Acetic acid, 2-(1-methylethyl)hydrazide → 1H-1,2,4-Triazole-5-carboxylic acid, 3-methyl-1-(1-methylethyl)-, ethyl ester

To a solution of ethyl thiooxamate (29.6 g, 0.22 mol) in DCM (260 mL) at RT was added trimethyloxonium tetrafluoroborate (34.5 g, 0.23 mol) and the mixture stirred at RT for 2 h. During this time the yellow colour faded and a thick white precipitate was formed. Acetic acid N′-isopropylhydrazide (27.1 g, 0.23 mol) and TEA (30.9 mL, 0.22 mol) were added as a solution in DCM (75 mL) causing the precipitate to dissolve. The reaction mixture was stirred at reflux for 5 h then at RT for 10 h. The reaction mixture was washed with water, and the aqueous layer extracted with DCM (2×50 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-100% ethyl acetate in cyclohexane) to give 2-Isopropyl-5-methyl-2H-[1,2,4]triazole-3-carboxylic acid ethyl ester as a pale yellow oil which crystallised on standing (15.6 g, 32%). 1H NMR 400 MHz (CDCl3) δ: 5.49 (1H, sept, J=6.7 Hz), 4.45 (2H, t, J=7.2 Hz), 2.43 (3H, s), 1.50 (6H, d, J=6.7 Hz), 1.44 (3H, t, J=7.2 Hz)

1. customa thick white precipitate was formed
2. dissolutionto dissolve
3. stirringThe reaction mixture was stirred
4. temperatureat reflux for 5 h
5. waitat RT for 10 h
6. washThe reaction mixture was washed with water
7. extractionthe aqueous layer extracted with DCM (2×50 mL)
8. washThe combined organic extracts were washed with brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated in vacuo

ORD record

ord-aad133ad5b854f3fbd644f06014ffb1d

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242104B2