3-(Trifluoromethyl)pyrazole

Colorless to light yellow liqui

Manufacture of 3-(trifluoromethyl) 1 H-pyrazole; To a solution of 4.4 moles hydrazine.hydrochloride in 2.2L of methanol in a 3 -necked flask, equipped with a mechanical stirrer, a reflux condenser and a dropping funnel an equimolar amount of ETFBO which had been manufactured by addition of trifluoroacetyl chloride to ethyl vinyl ether was added dropwise over about 4 hours under NStep 2: Preparation of 3-trifluoromethyl-lH-pyrazole 88a. To a stirred solution of hydrazine monochloride (6.62 g, 1.6 eq.) in EtOH (300 mL) was added dropwise To a stirred solution of hydrazine monochloride (6.62 g, 1.6 eq.) in EtOH (300 mL) was added dropwise compound 231 (10.16 g, 1 eq.) in EtOH (200 mL). The reaction mixture was refluxed for 6 hrs and evaporated to dryness. Water and EtOAc were added to the residue. The organic layer was washed with water and brine, dried over NaHydrazine dihydrochloride (225 g, 2.14 mol, 1.6 equivalents) was taken in ethanol (1.4 L) and stirred well, triethylamine (135.4 g (185.4 mL), 1.34 mol, 1 equivalent) was added drop wise for 45 min at room temperature. Then step-a product (225 g, crude) was added drop wise at room temperature and the overall reaction mixture was refluxed for overnight. Progress of the reaction was monitored by TLC (20 percent ethyl acetate/n-hexane). On completion of the reaction, ethanol was distilled off completely, residue was taken in ice water (500 mL) and the product extracted with ethyl acetate (2 * 400 mL). Combined extract was washed with ice water (300 mL), dried over sodium sulphate and concentrated under reduced pressure to yield the required product as and off white solid (195 g).Step b: Hydrazine dihydrochloride (225 g, 2.14 mol, 1.6 equivalents) was taken in ethanol (1.4 L) and stirred well. triethylamine (135.4 g (185.4 mL), 1.34 mol, 1 equivalent) was added drop wise for 45 min at room temperature. Then step-a product (225 g, crude) was added drop wise at room temperature and the overall reaction mixture was refluxed for overnight. Progress of the reaction was monitored by TLC (20percent ethyl acetate/n-hexane). On completion of the reaction, ethanol was distilled off completely, residue was taken in ice water (500 mL) and the product extracted with ethyl acetate (2Г—400 mL). Combined extract was washed with ice water (300 mL), dried over sodium sulfate and concentrated under reduced pressure to yield the required product as and off white solid (195 g).To the reaction flask was added successively (E)-4-ethoxy-1, 1, 1-trifluoro-3-buten-2-one (18.41 g, 109.51 mmol), ethanol (300 ml) and 85percent hydrazine hydrate (10.32 g, 175.21 mmol) and the reaction was heated to reflux. After the reaction was refluxed for 5 hours, the reaction solution was cooled to room temperature, concentrated under reduced pressure, to the residue was added water (150 ml), and extracted with ethyl acetate (2 × 300 ml), the organic layer was washed with saturated brine (200 ml) the latter was washed, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and the residue was purified by column chromatography (as eluent PE: EA = 20: 1 (v / v)), to give a yellow solid 9.87 g, yield 66.23percent.Step (ii): Synthesis of 3-trifluoromethyl-lH-Pyrazole (21); 20 21To a stirred solution of hydrazine dihydrochloride (1 gram, 9.6 mmol) in absolute ethanol (30 mL) was added a solution of 4-ethoxy- 1, 1, 1 -trifluoro-3-buten-2- one (20) (1.62 gram, 6 mmol) in ethanol (20 mL) dropwise under a nitrogen atmosphere. The mixture was refluxed for 6 hrs and then evaporated to dryness. The residue was treated with cold water (10 mL) followed by ethylacetate. The organic layer was collected, washed with water followed by saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under vacuum to give 3-trifluoromethyl-li7-Pyrazole as a low melting solid (21) (1.15 gm, 88percent yield);

3-(Trifluoromethyl)pyrazole was determined to be a small compound inhibitor of human FATP2.

Molecular Weight:136.08
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:136.02483259
Monoisotopic Mass:136.02483259
Topological Polar Surface Area:28.7
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes