Chemical Properties
Colorless to light yellow liqui
Uses
3-(Trifluoromethyl)pyrazole may be used in copper-catalyzed pyrazole
N-arylation. It may be used in the synthesis of sodium hydridotris(1
H-3-trifluoromethylpyrazol-1-yl)borate by heating with sodium borohydride.
Uses
3-(Trifluoromethyl)pyrazole was determined to be a small compound inhibitor of human FATP2.
Definition
ChEBI: 3-(Trifluoromethyl)-1H-pyrazole is a member of pyrazoles.
General Description
3-(Trifluoromethyl)pyrazoles is a heterocyclic building block. It undergoes alkylation with alkyl iodides in DMF to afford the
N-alkyl pyrazoles. It participates in the synthesis of disubstituted pyrimidines.
Synthesis
Example 2 Preparation of 3-(trifluoromethyl)-1H-pyrazole: In a three-necked flask equipped with a mechanical stirrer, a reflux condenser, and a dropping funnel, a solution of 4.4 moles of hydrazine hydrochloride dissolved in 2.2 L of methanol was added. Under nitrogen protection, an equimolar amount of (E)-1-ethoxy-3-trifluoromethyl-1,3-butadiene (ETFBO) was slowly added through the dropping funnel in a titration process for about 4 hours while the temperature of the reaction mixture was controlled to remain below 15 °C. After completion of the dropwise addition, the reaction mixture was refluxed for 12 hours. At the end of the reaction, the reaction solution was filtered and transferred to a 2L flask and concentrated under vacuum (another batch of reaction prepared in parallel under the same conditions, the total yield of the two batches of crude product was about 95%). After combining the two batches of crude product, purification was carried out by short-range vacuum distillation (27 mbar), resulting in 1105 g of pure product in 92% yield of the theoretical value.
References
[1] Patent: WO2010/37688, 2010, A1. Location in patent: Page/Page column 8
[2] Patent: WO2009/14730, 2009, A1. Location in patent: Page/Page column 131-132
[3] Patent: WO2011/17389, 2011, A1. Location in patent: Page/Page column 152
[4] Journal of Organic Chemistry USSR (English Translation), 1990, vol. 26, # 9.1, p. 1623 - 1628
[5] Zhurnal Organicheskoi Khimii, 1990, vol. 26, # 9, p. 1877 - 1883
