4-Hydroxy-6-(trifluoromethyl)pyrimidine synthesis
- Product Name:4-Hydroxy-6-(trifluoromethyl)pyrimidine
- CAS Number:1546-78-7
- Molecular formula:C5H3F3N2O
- Molecular Weight:164.09
6313-33-3
372-31-6
1546-78-7
Ethyl trifluoroacetoacetate (0.16 mL, 1.0 eq.) and DBU (0.19 mL, 1.2 eq.) were added to a three-necked flask, followed by the addition of anhydrous ethanol (10 mL) to dissolve the reactants. An ethanol solution of formamidine hydrochloride (0.09 g formamidine hydrochloride dissolved in 2 mL of ethanol, 1.05 equiv. of formamidine hydrochloride) was prepared and added to the reaction system. The reaction temperature was adjusted to 70-80 °C and maintained for 3-5 hours, during which the progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was diluted with water (20 mL) and the pH was adjusted to 6-7 with 1 mol/L hydrochloric acid.Subsequently, the aqueous phase was extracted with ethyl acetate (3 × 8 mL), the organic phases were combined and dried with anhydrous sodium sulfate. After filtration, the solvent was removed by vacuum distillation to give a light yellow solid. The solid was washed with petroleum ether (5 mL), filtered and the filter cake was washed with petroleum ether. Finally, the product was dried in an oven at 55 °C for 2 h to give a light yellow flaky solid in 96% yield.
Yield: 96%
Reaction Conditions:
with 1,8-diazabicyclo[5.4.0]undec-7-ene in ethanol at 70 - 80;
Steps:
2 (2) Synthesis of 4-hydroxy-6-trifluoromethylpyrimidine
To a three-necked flask was added ethyl trifluoroacetoacetate (0.16 mL, 1.0 eq.),DBU (0.19 mL, 1.2 eq.),Add absolute ethanol (10 mL) to dissolve.A solution of formamidine hydrochloride in ethanol (0.09 g of formamidine hydrochloride in 2 mL of ethanol,The amount of formamidine hydrochloride1.05 eq.).Dropping the temperature to 70-80 ° C for 3 to 5 hours.TLC monitoring,The reaction was complete.The solvent was distilled off under reduced pressure,Diluted with water (20 mL)With 1mol / L hydrochloric acid adjusted pH = 6 ~ 7,Extraction with ethyl acetate (3 x 8 mL)The organic phase was combined with anhydrous sulfuric acidSodium drying, filtration, vacuum distillation of the solvent was light yellow solid, add petroleum ether (5mL) shock, filter, filter cake washed with petroleum ether,The oven was dried at 55 ° C for 2 hours to give a pale yellow flake solid in 96% yield.
References:
China Pharmaceutical University;Dai, Zhenya;Xu, Pei;Yu, Qiuhan;Zhao, Yunde CN106188013, 2016, A Location in patent:Paragraph 0012; 0013; 0019
6313-33-3
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1546-78-7
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$9.00/1g