Ethyl 1-(2-Morpholinoethyl)-1H-Pyrazole-4-Carboxylate synthesis

Yield:874196-88-0 70%

Reaction Conditions:

Stage #1: N-(2-chlorethyl)morpholine;1H-pyrazole-4-carboxylic acidwith potassium carbonate in DMF (N,N-dimethyl-formamide) at 20 - 75; for 24.5 h;
Stage #2: with water in DMF (N,N-dimethyl-formamide);

Steps:

30 1-(2-Morpholin-4-yl-ethyl)-1H-pyrazole-4-carboxylic acid ethyl ester

1H-Pyrazole-4-carboxylic acid (300 mg, 2.1 mmol), 4-(2-chloroethyl)morpholine (822 mg, 4.3 mmol) and potassium carbonate (1.2 g, 8.6 mmol) are dissolved in dimethylformamide (12 ml) and stirred for 6.5 h at 75° C. Aftr stnding for another 18 h at ambient temperature, the reaction mixture was treated with water (25 ml) and extracted four times with ethyl acetate (25 ml each). The combined organic layers are extracted four times with water, dryed with magnesium sulphate and evaporated in vacuo. Flash chromatography (silice, eluent dichloromethane containing 4% methanol) afforded the title compound as colorles liquid (70% yield). MS: m/e=254(M+H⁺). Following the general method of example 30 the compounds of examples 31 to 32 were prepared.

References:

US2006/19949,2006,A1 Location in patent:Page/Page column 10-11