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Structure of 59938-06-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 59938-06-6 |
Formula : | C6H7F3O2 |
M.W : | 168.11 |
SMILES Code : | O=C(/C=C/OCC)C(F)(F)F |
MDL No. : | MFCD00192131 |
InChI Key : | YKYIFUROKBDHCY-ONEGZZNKSA-N |
Pubchem ID : | 5709222 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H225-H315-H319 |
Precautionary Statements: | P210-P233-P240-P241+P242+P243-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P403+P235-P501 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.7% | Stage #1: for 3 h; Reflux; Sealed tube Stage #2: With sodium ethanolate In ethanol for 5 h; Reflux; Sealed tube |
In the 1000 mL sealed four-mouth reaction bottle, the above Example 1 was added.168.1 g of 4-ethoxy-1,1,1-trifluoro-3-en-2-one, 68.1 g of 3-aminoacrylonitrile, and 300 mL of solvent ethanol.Stir well, heat to reflux for 3 hours, then add 59.4 g of sodium ethoxide in ethanol and reflux for 5 hours.Recovery of solvent methanolThe white solid was washed with water to give 166.4 g of 4-trifluoromethylnicotinonitrile in a yield of 96.7percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24 g | at 55℃; for 20 h; Cooling with ice | ETFBO (270 g, 1.61 mol, 1.00 eq) was dissolved in methanol (750 mL). The solution was cooled in an ice/water-bath and methyl hydrazine (88.3 mL, 77.7 g, 1.69 mol, 1.05 eq) was added dropwise within 20 minutes. The mixture was heated to 55°C and stirred at this temperature for 20 h in dry air (drying tube). Successively the solvent was removed and the residue distilled under vacuum : 1st Fraction : 150 mbar, 130°C bath temperature, 73~85°C, mixture of isomers, 129 g.2nd Fraction : 70 mbar, 150°C bath temperature, 75~85°C, 1-methyl-3-(trifluoromethyl)-1H-pyrazole, 24 g. Overall yield : 153 g (1.02 mol) 63 percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24 g | at 55℃; for 20 h; Cooling with ice | The solution was cooled in an ice/water-bath and methyl hydrazine (88.3 mL, 77.7 g, 1.69 mol, 1.05 eq) was added dropwise within 20 minutes. The mixture was heated to 55°C and stirred at this temperature for 20 h in dry air (drying tube). Successively the solvent was removed and the residue distilled under vacuum : 1st Fraction : 150 mbar, 130°C bath temperature, 73~85°C, mixture of isomers, 129 g. 2nd Fraction : 70 mbar, 150°C bath temperature, 75-85 °C, l-methyl-3-(trifluoro- methyl)-lH-pyrazole, 24 g. Overall yield : 153 g (1.02 mol) 63 percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With sodium hydride In tetrahydrofuran at 0℃; for 4 h; | 4-Ethoxy-1,1, 1-trifluoro-3-buten-2-one (5g, 29.7 mmol) followed by 2,4-pentadione (3. 05ML, 29. 7MMOL) were added to a cooled 0 C suspension of NaH (2.38g, 59.4 mmol) in THF (120 mL). The reaction mixture was REFLUXED for 4 hrs and then partitioned between 1 N HCI and EtOAc. The organic layers were washed with brine, dried over NA2SO4 and concentrated to a red oil. Purification by flash column chromatography (0percent to 10percent EtOAc in hexanes) gave the title compound as a yellow oil (1.73g, 29percent). H NMR (400 MHz, CDC13) : 5 2.69 (s, 3 H), 7.15 (d, J=9.9 Hz, 1 H), 7.25 (s, 1 H), 7.86 (d, J=8.3 Hz, 1 H), 12.29 (s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; for 4h;Heating / reflux; | To a mixture of 18 g of 4-ethoxy-1,1,1-trifluoro-3-butene-2-one and 50 ml of methanol was added 5.7 ml of methylhydrazme, and the mixture was heated to 'reflux for 4 hours. The reaction mixture was allowed to cool to room temperature, concentrated under reduced pressure, and subjected to distillation under reduced pressure (60C/15 mmHg) to obtain 8.71 g of l-methyl-3-trifluoromethyl-lH-pyrazole of the formula:l-Methyl-3-trifluoromethyl-lH-pyrazole 1 H-NMR ( CDCl3 , TMS ) delta (ppm) : 3 . 97 ( 3H, s ) , 6 . 51 ( IH, d, J=2Hz ) ,7 . 40 ( IH , d, J=2Hz ) . | |
In methanol;Reflux; | Chemical synthesis of compound 16677. For synthesis of compound 16677, 1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid 3 (Scheme 1, FIG. 10) was prepared from commercially available compound 1 as previously described (Schlosser et al., (2002) Eur. J. Org. Chem. 2002(17), 2913-2920). Compound 3 (820 mg, 4.2 mmol) in dichloromethane (10 ml) was treated with oxalyl chloride (2.0 M in CH2Cl2, 8.5 mmol, 4.2 ml) and a catalytic amount of DMF. The reaction mixture was incubated at room temperature for 5 hours. Evaporation of solvent delivered yellow acyl chloride 4 in quantitative yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With hydrogenchloride; potassium tert-butylate; In tetrahydrofuran; | Preparation of 3-(2,4-difluorophenyl)-6-trifluoromethyl-2H-pyran-2-one (Intermediate No. 17-1) 7.7 g (69 mmol) of potassium tert-butoxide was dissolved in 200 ml of THF, and 10 g (65 mmol) of 2,4-difluorophenyl acetonitrile was dropwise added thereto under cooling with ice. Ten minutes later, 13.5 g (69 mmol) of (E)-4-ethoxy-1,1,1-trifluoro-3-buten-2-one was dropwise added thereto, followed by stirring at room temperature for 4 hours. THF was distilled off under reduced pressure. Then, the obtained residue was poured into water, acidified to pH 1 with 1N hydrochloric acid and then extracted with ethyl acetate. After washing with water and an aqueous sodium hydrogencarbonate solution, the organic layer was dried over anhydrous magnesium sulfate. And then, the ethyl acetate was distilled off under reduced pressure. To the obtained residue, 150 ml of concentrated hydrochloric acid was added, followed by stirring for 4 hours under heating and refluxing. This reaction solution was poured into ice water and extracted with ethyl acetate, followed by washing with water. The organic layer was dried over anhydrous magnesium sulfate, and then, ethyl acetate was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 13.8 g (yield: 76%) of the desired product. Melting point: 98-100 C. 1 H-NMR (400 MHz,CDCl3) deltavalue: 6.78(1H,d), 6.95(2H,m), 7.52(1H,d), 7.56(1H,q)ppm |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24 g | at 55℃; for 20h;Cooling with ice; | The solution was cooled in an ice/water-bath and methyl hydrazine (88.3 mL, 77.7 g, 1.69 mol, 1.05 eq) was added dropwise within 20 minutes. The mixture was heated to 55C and stirred at this temperature for 20 h in dry air (drying tube). Successively the solvent was removed and the residue distilled under vacuum : 1st Fraction : 150 mbar, 130C bath temperature, 73~85C, mixture of isomers, 129 g. 2nd Fraction : 70 mbar, 150C bath temperature, 75-85 C, l-methyl-3-(trifluoro- methyl)-lH-pyrazole, 24 g. Overall yield : 153 g (1.02 mol) 63 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24 g | In methanol; at 55℃; for 20h;Cooling with ice; | ETFBO (270 g, 1.61 mol, 1.00 eq) was dissolved in methanol (750 mL). The solution was cooled in an ice/water-bath and methyl hydrazine (88.3 mL, 77.7 g, 1.69 mol, 1.05 eq) was added dropwise within 20 minutes. The mixture was heated to 55C and stirred at this temperature for 20 h in dry air (drying tube). Successively the solvent was removed and the residue distilled under vacuum : 1st Fraction : 150 mbar, 130C bath temperature, 73~85C, mixture of isomers, 129 g.2nd Fraction : 70 mbar, 150C bath temperature, 75~85C, 1-methyl-3-(trifluoromethyl)-1H-pyrazole, 24 g. Overall yield : 153 g (1.02 mol) 63 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In methanol; at 40℃; | To a solution of (3E)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one (29.0 g, 172.50 mmol) in methanol (300 mL) was added methylhydrazine sulfuric acid (39.8 g, 276.10 mmol) portionwise, followed by the addition of triethylamine (18.0 g, 177.88 mmol) portionwise. The resulting solution was stirred overnight at 40 C. The resulting mixture was then cooled to room temperature and concentrated under vacuum. The reaction was then quenched by the addition of ice water (200 mL) and was extracted with Et2O (3×200 mL). The combined organic layers were washed with brine (2×200 mL), dried over anhydrous MgSO4, filtered and concentrated to provide the desired product as a light brown oil (29.0 g, crude) which was used as is in the next reaction. LC-MS (ES, m/z): 151.0 [M+H]+, 192.0 [M+H+CH3CN]+; 1H NMR (300 MHz, CDCl3): delta 7.37 (m, 1H), 6.48 (d, J=2.2 Hz, 1H), 3.94 (s, 3H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86 g | In water; at 100℃; for 8h; | Methyl hydrazine sulfate 170g,B 170g was added dropwise with stirring.The temperature was further raised to 100 C for 8 hours.Cool to room temperature,Divide the organic phase,The aqueous phase is extracted once with DCM.Wash once with saturated sodium chloride,Dry over anhydrous sodium sulfate,concentrate. Vacuum distillation,The product is cooled and received with an ice salt bath.External temperature 50 C,Internal temperature 38 C,0.5 Torr,A colorless liquid 86g. |
Tags: 59938-06-6 synthesis path| 59938-06-6 SDS| 59938-06-6 COA| 59938-06-6 purity| 59938-06-6 application| 59938-06-6 NMR| 59938-06-6 COA| 59938-06-6 structure
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