Hydrochloric Acid → Methyl 2-(4-acetyl-5-methyl-1H-pyrazol-1-yl)acetate

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Reaction Steps

To a solution of 3-(ethoxymethylene)pentane-2,4-dione (Perkin 1. 2000, 1455-1460, 1.95 g, 12.5 mmol) in MeOH (33 mL) was added a solution of ethyl hydrazinoacetate hydrochloride (2.09 g, 13.5 mmol) and conc.HCl (2.6 ml) in MeOH (10 ml) (pre-cooled to 0° C.) dropwise at −15° C. The resulting mixture was then stirred for 24 hours at room temperature. After removal of the solvent at room temperature, the residue was basified with 2N NaOH aq, and the aqueous layer was extracted several times with EtOAc. The combined organic extracts were dried over Na2SO4, and concentrated in vacuo. The aqueous layer was acidified to pH 1 with 2N HCl aq. and extracted with EtOAc 6 times. The combined organic extracts were dried over Na2SO4, and concentrated in vacuo to give the crude 2-(4-acetyl-5-methyl-1H-pyrazol-1-yl)acetic acid as a mixture of regioisomers (1.17 g, <51% yield). 1H NMR (300 MHz, DMSO-d6) δ 2.37 (3H, s), 2.43 (3H, s), 4.99 (2H, s), 7.81 (1H, s), 13.2 (1H, brs).

Provenance & Evidence