4-Chloro-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester synthesis

Yield: 96%

Reaction Conditions:

with N-chloro-succinimide in N,N-dimethyl-formamide at 20; for 24 h;

Steps:

D.1 Preparation of 4-Chloro-5-methyl-lH-pyrazole-3-carboxylic acid ethyl ester.
A mixture of 5-methyl-lH-pyrazole-3-carboxylic acid ethyl ester (4.45 g, 28.9 mmol) and N-chlorosuccinimide (5.01 g, 37.5 mmol) in dimethylformamide (60 mL) was stirred for 24 hours at ambient temperature. The reaction was then concentrated down and purified by eluting through a silica gel column with a 0 to 100% ethyl acetate / heptane gradient to afford the title compound (5.2 g, 96% yield) as a white solid. MS (ESI) [m/e, (M+H)⁺] = 189.3. ¹H NMR (400 MHz, chloroform-d) δ ppm 9.39 (br. s., 1 H), 4.44 (q, J=7.1 Hz, 2 H), 2.35 (s, 3 H), 1.43 (t, J=7.1 Hz, 3 H). [00227]

References:

NOVARTIS AG;VISSER, Michael Scott;YUSUFF, Naeem WO2013/96049, 2013, A1 Location in patent:Paragraph 00232