1H-1,2,4-Triazole-5-carboxylic acid, 3-Methyl-1-(1-Methylethyl)-, ethyl ester synthesis

Yield:1282517-47-8 665 mg

Reaction Conditions:

Stage #1: 5-methyl-2H-[1,2,4]triazole-3-carboxylic acid ethyl esterwith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 0.5 h;
Stage #2: 2-iodo-propane in N,N-dimethyl-formamide;mineral oil at 25; for 14 h;

Steps:

473.1 Step-1, ethyl 2-isopropyl-5-methyl-1,2,4-triazole-3-carboxylate

NaH (309.4 mg, 7.73 mmol, 60% dispersion in mineral oil) was added to a stirred solution of ethyl 5-methyl-2H-1,2,4-triazole-3-carboxylate (1.00 g, 6.45 mmol) in DMF (10.00 mL). The resulting mixture was stirred at 0 °C for 30 min, then 2-iodopropane (1.64 g, 9.67 mmol) was added to the reaction mixture. The resulting mixture was stirred at 25 °C for 14 h. The resulting mixture was diluted with EtOAc and washed with water. The organic layers were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with DCM/MeOH (20/1 v/v) to obtain the title compound (665.0 mg) as an oil. LCMS (ESI): 198.1 [M+H]⁺.

References:

WO2022/99144,2022,A1 Location in patent:Paragraph 4191-4193