Application of 950858-65-8, A common heterocyclic compound, 950858-65-8, name is 1-tert-Butyl-1H-pyrazole-4-carboxylic acid, molecular formula is C8H12N2O2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Step 3: 1-tert-Butyl-5-chloro-1H-pyrazole-4-carboxylic acid tert-butyl-1H-pyrazole-4-carboxylic acid (5 g, 29.73 mmol) was dissolved in tetrahydrofuran (50 ml) at room temp. In a separate flask was added n-butyllithium (2.5M solution in hexane, 29.73 ml, 74.33 mmol) and was cooled to -15° C. The 1-tert-butyl-1H-pyrazole-4-carboxylic acid solution was added dropwise to the n-Butyllithium solution, maintaining internal temperature below -10° C. The total addition time lasted 30 min. The resulting brownish suspension was stirred and maintained between -10° C. and -15° C. for 40 min. The reaction was then cooled to -15° C. to -20° C. A solution of hexachloroethane (14.08 g, 59.46 mmol) in tetrahydrofuran (50 ml) was added dropwise, maintaining internal temperature below -10° C. The total addition time lasted 20 min. After the addition, the resulting dark brownish solution was stirred at -10° C. to -15° C. for 30 min and was warmed up to room temp. over 1 h. The reaction mixture was then cooled to 15° C. and water (50 ml) was added slowly, maintaining internal temperature below 20° C. 120 ml of organic solvents were distilled under reduced pressure at 25° C. water bath leading to a suspension. Heptane (50 ml) was added leading to a clear brownish biphasic solution. After stirring at room temp. for 15 min, the aqueous layer (pH=11.8) was separated. The organic layer was extracted once with NaOH (1N, 20 ml). The combined aqueous phase was washed with heptane (25 ml) and was cooled in an ice-bath. Hydrochloric acid (6N) was added to adjust pH=2, maintaining internal temperature below 20° C. The suspension was stirred in the ice-bath at 0-5° C. for 1 h and the solid was filtered and washed with water (40 ml). After drying in vacuo at 60° C. for 18 h, 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid (5.28 g) was obtained as a light yellow solid.
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; Anderson, Kevin William; Fotouhi, Nader; Gillespie, Paul; Goodnow, Robert Alan; Guertin, Kevin Richard; Haynes, Nancy-Ellen; Myers, Michael Paul; Pietranico-Cole, Sherrie Lynn; Qi, Lida; Rossman, Pamela Loreen; Scott, Nathan Robert; Thakkar, Kshitij Chhabilbhai; Tilley, Jefferson Wright; Zhang, Qiang; US2007/225280; (2007); A1;,
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