ChemicalBook CAS DataBase List 1-METHYL-5-(TRIFLUOROMETHYL)-1H-PYRAZOLE-4-CARBOXYLIC ACID

1-METHYL-5-(TRIFLUOROMETHYL)-1H-PYRAZOLE-4-CARBOXYLIC ACID synthesis

6synthesis methods

Product Name:1-METHYL-5-(TRIFLUOROMETHYL)-1H-PYRAZOLE-4-CARBOXYLIC ACID
CAS Number:119083-00-0
Molecular formula:C6H5F3N2O2
Molecular Weight:194.11

Ethyl 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

231285-86-2

119083-00-0

The general procedure for the synthesis of 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid from ethyl 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate is as follows: Preparation of intermediate 65b: Ethyl 1-methyl-5-(trifluoromethyl)pyrazole-4-carboxylate (2.91 g, 13.0 mmol) was dissolved in THF (52 mL) and cooled to 0 °C. Subsequently, a solution of lithium hydroxide (627 mg, 26.1 mmol) in water (26 mL) was slowly added. The reaction mixture was stirred overnight at room temperature. After completion of the reaction, the mixture was acidified to pH 1-2 with 1 M HCl and extracted with EtOAc (4 x 50 mL). The organic layers were combined, washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 1-methyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid (2.39 g, 12.33 mmol, 94% yield) as an off-white solid. The product characterization data are as follows: 1H NMR (CDCl3, 400 MHz) δ/ppm: 8.02 (1H, s), 4.13 (3H, q, J = 2.0 Hz) Exchangeable protons. 19F NMR (CDCl3, 400 MHz) δ/ppm: -57.2. MS Method 2: RT: 1.16 min, m/z 193.0 [M-H]-.

231285-86-2 Synthesis

231285-86-2
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$24.00/100mg

119083-00-0
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$62.00/250mg

Yield: 94%

Reaction Conditions:

with water;lithium hydroxide in tetrahydrofuran at 0 - 20;

Steps:

Intermediate 65b: I -methyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid
[00618] Intermediate 65b: I -methyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid[00619] To a solution of ethyl 1 -methyl-5-(trifluoromethyl)pyrazole-4-carboxylate (2.91 g, 13.Ogmmol) in THF (52mL) at 0 °Cwas added a solution of lithium hydroxide (627mg, 26.l8mmol) in water (26mL) and the mixture was stirred at room temperature overnight. The mixture was thenacidified to pH 1-2 with 1M HCI and extracted with EtOAc (4 x 5OmL). The combined organic layers were washed with brine (5OmL), dried over Na2SO4, filtered and concentrated in vacuo to give 1- methyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid (2.39g, 12.33mmol, 94% yield) as an off-white solid.1H NMR (CDCI3, 400MHz) O/ppm: 8.02 (1H, 5), 4.13 (3H, q, J= 2.0Hz) exchangeable proton notseen. 19F NMR (CDCI3, 400MHz) O/ppm: -57.2.MS Method 2: RT: 1.16 mi mlz 193.0 [M-H]

References:

REDX PHARMA PLC;ARMER, Richard;BELFIELD, Andrew;BINGHAM, Matilda;JOHNSON, Alice;MARGATHE, Jean-Francois;AVERY, Craig;HUGHES, Shaun;MORRISON, Angus WO2016/51193, 2016, A1 Location in patent:Paragraph 00615; 00618; 00619