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CAS No. : | 381-88-4 | MDL No. : | MFCD00190641 |
Formula : | C4H5F3O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | QBVHMPFSDVNFAY-UHFFFAOYSA-N |
M.W : | 126.08 | Pubchem ID : | 238288 |
Synonyms : |
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 21.73 |
TPSA : | 17.07 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.98 cm/s |
Log Po/w (iLOGP) : | 1.39 |
Log Po/w (XLOGP3) : | 1.53 |
Log Po/w (WLOGP) : | 2.79 |
Log Po/w (MLOGP) : | 1.2 |
Log Po/w (SILICOS-IT) : | 1.6 |
Consensus Log Po/w : | 1.7 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 3.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.45 |
Solubility : | 4.44 mg/ml ; 0.0352 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.5 |
Solubility : | 4.01 mg/ml ; 0.0318 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.47 |
Solubility : | 4.32 mg/ml ; 0.0343 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P210 | UN#: | 1993 |
Hazard Statements: | H225 | Packing Group: | Ⅱ |
GHS Pictogram: |
* 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 |
---|---|---|
93% | With N-Bromosuccinimide; Perbenzoic acid In tetrachloromethane for 36h; Heating; Irradiation; | |
32% | With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 70℃; for 36h; Irradiation with a tungsten lamp; | 1.1G A suspension of l,l,l-trifluoro-butan-2-one (10 g, 79.4 mmoles), N- bromosuccinimide (36.7 g, 206.3 mmoles) and benzoyl peroxide (25 mg, 0.1 mmoles) in carbon tetrachloride (100 ml) was irradiated at 70 0C with a tungsten lamp for 36 hours. The suspension was filtered and the filtrate was evaporated in vacuo. The residue was triturated with petrol, filtered and the filtrate was evaporated in vacuo to give 3,3-dibromo-l,l,l-trifluoro-butan-2-one as a pale yellow liquid (13.5 g, 32%) which was a 1:1 mixture of the desired product with residual NBS. The crude product was taken into the next step without purification. |
With bromine; sodium acetate; acetic acid |
With sulfuric acid; bromine; sodium acetate In acetic acid | R.1 REFERENCE EXAMPLE 1 REFERENCE EXAMPLE 1 This is a production example for 3,3-dibromo-1,1,1-trifluoro-2-butanone used in Production Example 13. First, 34.0 g of sodium acetate was dissolved in 270 ml of acetic acid, to which 25 g (0.20 mol) of 1,1,1-trifluoro-2-butanone was added, and while keeping the temperature at 15° to 20° C., 66.3 g (0.42 mol) of bromine was added dropwise over 45 minutes. The reaction mixture was stirred for 5 hours, while keeping the temperature at 15° to 20° C., and then allowed to stand at room temperature for 68 hours. The supernatant was taken and washed with 600 ml of concentrated sulfuric acid. Further washing with 307 ml of concentrated sulfuric acid and distillation under normal pressure gave 28 g (0.10 mol) of 3,3-dibromo-1,1,1-trifluoro-2-butanone. STR56 | |
With bromine; sodium acetate; acetic acid at 15 - 20℃; for 73.75h; | 1 Reference Example 1 Reference Example 1 This is a production example for 3,3-dibromo-1,1,1-trifluoro-2-butanone used in Production Example 13. First, 34.0 g of sodium acetate was dissolved in 270 ml of acetic acid, to which 25 g (0.20 mol) of 1,1,1-trifluoro-2-butanone was added, and while keeping the temperature at 15° to 20° C., 66.3 g (0.42 mol) of bromine was added dropwise over 45 minutes.. The reaction mixture was stirred for 5 hours, while keeping the temperature at 15° to 20° C., and then allowed to stand at room temperature for 68 hours.. The supernatant was taken and washed with 600 ml of concentrated sulfuric acid.. Further washing with 307 ml of concentrated sulfuric acid and distillation under normal pressure gave 28 g (0.10 mol) of 3,3-dibromo-1,1,1-trifluoro-2-butanone. . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; bromine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.2% | With methanesulfonic acid; trifluoroacetic acid at 120℃; for 3h; | 1 Example 1 In 500mL equipped with distillation column,Magnetic stirrer and thermometer in a glass reactor were charged with 0.6 mol of anhydrous methanesulfonic acid,Start stirring,At an internal temperature of 120 ° C,1.0 mol was added dropwise ethyl 2-methyl-4,4,4-trifluoroacetoacetate and 1.0 mol of trifluoroacetic acid,Dropping time for 3h,The product 1,1,1-trifluoro-2-butanone was recovered at a reflux ratio of 1: 1And ethyl trifluoroacetate. To obtain 120 g of 1,1,1-trifluoro-2-butanone in an amount of 99.2%The yield was 95.2%.To obtain 132 g of ethyl acetate trifluoroacetate in an amount of 99.9%The yield was 93.0%. |
With sulfuric acid; acetic acid | ||
(i) Na, Et2O, (ii) aq. H2SO4; Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With formic acid; tetrabutylammomium bromide; water; potassium formate at 30℃; for 21h; Inert atmosphere; Autoclave; | 36 Example 36 Under argon gas atmosphere, a ruthenium complex RuCl[(S,S)-Tsdpen](mesitylene) (61.1 mg, 0.10 mmol), potassium formate (5.1 g, 60.9 mmol), tetrabutylammonium bromide (TBAB) (0.47 g, 1.5 mmol), water (6.0 mL), formic acid (0.11 mL, 2.9 mmol; 0.1 equivalent relative to the ketone used) and 1,1,1-trifluoro-2-butanone (4.0 mL, 29 mmol, substrate/catalyst ratio: 300) were introduced in a 100-mL glass autoclave. The container was sealed and stirred at 30°C for 21 h. After the reaction was complete, the reaction solution was collected with dimethyl sulfoxide (DMSO), and GC was measured by adding N,N-dimethylformamide (1.0 mL, 12.9 mmol) as the internal standard material. The conversion obtained from the amount of remaining ketone substrate was 100%. Optical purity was 96.4%ee. We confirmed that the reaction can proceed well with 1,1,1-trifluoro-2-butanone as well. |
28% | With sodium tetrahydroborate In diethyl ether; water at 0 - 32℃; for 16h; | 11 A41: l,l,l-trifluorobutan-2-ol To a solution of l,l,l-trifluorobutan-2-one (30 g, 237.94 mmol) in ether (300 mL) and water (10 mL) was added a solution of NaBLL (9.0 g, 237.94 mmol) in water (40 mL) in portions at 0 °C. The mixture was stirred at 32 °C for 16 hours. 0.5 M HC1 was added to acidify to pH 6. The aqueous layer was extracted with EtOAc (100 mL x 3). The combined organic layers were washed with brine (100 mL), dried over anhydrous NaiSCL, filtered and concentrated under reduced pressure. The crude product was distilled under reduced pressure (water pump, bp 75~80°C) to afford the product (12 g, 67.45 mmol, 28% yield) as an oil. *H NMR (400 MHz, CDCh) dH = 3.90-3.78 (m, 1H), 2.80-2.60 (m, 1H), 1.83-1.70 (m, 1H), 1.60-1.55 (m, 1H), 1.07 (t, 3H). |
With lithium aluminium tetrahydride In diethyl ether |
With sodium tetrahydroborate In water Ambient temperature; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium hydroxide; hydroxylamine hydrochloride In water for 4h; Heating; | |
With hydroxylamine hydrochloride; sodium acetate In water at -5 - 20℃; Large scale; | General procedure General procedure: Hydroxylamine hydrochloride (3.7 Kg, 53 mol) was added toa solution of sodium acetate (5.3 Kg, 64 mol) in 20 L water. Subsequently, 1,1,1-trifluoroacetone (3 Kg, 26.8 mol) was dosed within 0.5 h at a temperature range of -5 to + 10 °C. The reaction mixture was stirred at room temperature overnight.The crude oxime was diluted with a solution of sodium carbonate (0.7 Kg) in 5 L water and then separated. The low-boiling-point substances were then removed under reduced pressureto yield a pale yellow solid which was used for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.68 mmol | With ethene; dihydrogen peroxide In water at 75 - 80℃; for 24h; Further byproducts given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 0.80 mmol 2: 0.15 mmol | With tetraethyllead(IV) at 90℃; for 24h; Further byproducts given; | |
1: 0.33 mmol 2: 0.68 mmol | With ethene; dihydrogen peroxide In water at 90℃; for 24h; Further byproducts given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diethyl ether at 50 - 60℃; for 24h; Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: Ethyl isocyanoacetate With potassium <i>tert</i>-butylate In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61 % Spectr. | With titanium(IV) isopropylate In hexane at 20℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With gallium(III) triflate In dichloromethane at 100℃; for 7h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With phosphotungstic acid In toluene at 50℃; for 5h; Inert atmosphere; Sealed tube; | |
89% | With gallium(III) triflate In dichloromethane at 50℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With Nafion-H In dichloromethane at 120℃; for 6h; | |
80% | With gallium(III) triflate In dichloromethane at 50℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With Nafion-H In dichloromethane at 120℃; for 4h; | |
87% | With phosphotungstic acid In toluene at 50℃; for 5h; Inert atmosphere; Sealed tube; | |
83% | With gallium(III) triflate In dichloromethane at 50℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With Nafion-H In dichloromethane at 120℃; for 5h; | |
60% | With gallium(III) triflate In dichloromethane at 75℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With gallium(III) triflate In dichloromethane at 50℃; for 4h; | |
73% | With Nafion-H In dichloromethane at 120℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In acetonitrile at -40℃; for 96h; Title compound not separated from byproducts.; | ||
With (ΔS,S,S)-[Binolam3La(OTf)3]; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In acetonitrile at -40℃; for 96h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; | ||
18 % ee | With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((2R,2'R)-(Z)-(Sa,Sa)-6'-((4-(dimethylamino)pyridin-2-yl)amino)-2,2',4,4',7,7'-hexamethyl-2,2',3,3'-tetrahydro-[1,1'-biindenylidene]-6-yl)thiourea In toluene at -25℃; Overall yield = 70 %; |
54 % ee | With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((2R,2'R)-6'-((4-(dimethylamino)pyridin-2-yl)amino)-2,2',4,4',7,7'-hexamethyl-2,2',3,3'-tetrahydro-[1,1'-biindenylidene]-6-yl)thiourea In toluene at -25℃; Overall yield = 72 %; | |
90 % ee | With (R)-1-(1,1-bis(3,5-di-tert-butylphenyl)-3-(dimethylamino)-1-methoxypropan-2-yl)-3-(3,5-bis(trifluoromethyl)phenyl)urea In 2-methyltetrahydrofuran at -20℃; for 48h; Overall yield = 91 percent; enantioselective reaction; | 3. General Procedure for the Enantioselective Henry Reaction and characterization data for products 2 General procedure: A mixture of α-trifluoromethyl ketones 1 (0.2 mmol, 1.0 equiv.), catalyst 4l (0.01 mmol, 5 mol%) and nitroalkanes (2.0 mmol, 10.0 equiv.) were dissolved in 2-Me-THF (1.0 mL). The resulting mixture was stirred for 48 h at -20 °C until the reaction finished (monitored by TLC). The crude products were purified by flash column chromatography on silica gel (VPE / VEA = 6 : 1) to yield pure products 2a-2q. The enantiomeric excess of the product was determined by chiral HPLC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | at 80℃; for 2h; Microwave irradiation; | |
With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at 20℃; | ||
With potassium carbonate In dichloromethane at 20 - 30℃; | General procedure: To a solution of the trifluoromethyl ketone (14.4 mmol) in MeNO2 (14.4 mmol) was added granularpotassium carbonate 2g in CH2Cl2 (60 mL). The mixture was stirred for overnight at 20-30. After thereaction was completed, water (20 mL) was added, successively with 1N HCl to adjust pH to 5-6. Theorganic phase was separated and the aqueous phase was extracted with CH2Cl2 (20 mL * 2). Thecombined organic phase was washed with water (20 mL) then dried (Na2SO4). Removal of the solventunder reduced pressure gave an oily residue of the corresponding crude nitroalcohol, which was usedwithout further purification. |
With triethylamine at 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water | 6 EXAMPLE 6 The butyric acid used as starting material may be obtained as follows: 1,1,1,-Trifluorobutan-2-one (14 g.) is added dropwise to a stirred solution of potassium cyanide (8.2 g.) in water (30 ml.) which is maintained at 0° C. 25% V/v aqueous sulphuric acid (50 ml.) is added and the mixture is stirred at laboratory temperature for 16 hours and is then extracted with ether. The extract is washed with water, dried and evaporated to dryness and the residual oil is added dropwise to concentrated sulphuric acid (6 ml.) which is maintained at 70°-75° C. Water (50 ml.) is added and the mixture is heated at 95°-100° C. for 72 hours, cooled and extracted with ether. The ethereal extract is washed with water and then extracted with saturated aqueous sodium bicarbonate solution. The extract is acidified with equeous hydrochloric acid and then extracted with ether. The ethereal extract is washed with water, dried and evaporated to dryness and the residue is crystallized from a mixture of chloroform and petroleum ether (b.p. 60°-80° C.). There is thus obtained 2-hydroxy-2-trifluoromethylbutyric acid, m.p. 95°-100° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78℃; for 4h; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane | 1.1 Step 1: 3-(trifluoromethyl)-1-(trimethylsilyl)pent-1-yn-3-ol Step 1: 3-(trifluoromethyl)-1-(trimethylsilyl)pent-1-yn-3-ol To a solution of trimethylsilylacetylene (6.0 g, 61.1 mmol) in THF (80 mL) cooled at -78° C., a 1.6M n-butyllithium in hexanes (38 mL, 61.1 mmol) was added dropwise. The solution was then stirred 1 hour, before a solution trifluoromethylethylketone (10 g, 79.4 mmol) in 25 mL of THF was added slowly. The reaction was stirred at -78° C. for 4 hours. The reaction was then poured into a saturated ammonium chloride solution and the aqueous layer was extracted (4*) with diethyl ether. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue obtained was used as such for the next step. 1H NMR (400 MHz, acetone-d6): 5.83 (s, 1H), 1.80 (q, 2H), 1.14 (t, 3H), 0.18 (s, 9H). | |
Stage #1: trimethylsilylacetylene With n-butyllithium In tert-butyl methyl ether at -67 - -50℃; for 1.75h; Stage #2: 1,1,1-trifluoro-2-butanone In tert-butyl methyl ether at -50℃; for 1.33333h; | 1.A.1 EXAMPLE 1A Alternate Method for the Preparation of (S)-4-(3-fluorophenyl)-7-({4-[1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-2H-chromen-2-one Step 1. Alternate Method for the Preparation of (5)-4-(3-fluorophenyl)-7-({4-[1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-2H-chromen-2-one A 100 mL flask equipped with a mechanical stirrer, a thermocouple, a nitrogen inlet and a cooling bath was charged with trimethylsilyl acetylene (3.5 g, 1.50 eq) and MTBE (12.0 mL). The mixture was cooled to -67° C. and 2.26 M n-BuLi (11.2 mL, 1.05 eq) was added to the solution over 1 hr, keeping the reaction mixture below -50° C. The reaction mixture was aged 45 min before the addition of 1,1,1-trifluoro-2-butanone (3.3 mL, 1.00 eq) over a period of 1 hr (internal temperature was kept below -50° C.). The mixture was aged 20 min, then p-nitrobenzoyl chloride (4.7 g, 1.05 eq) was added over 1 hr as a THF solution (7.0 mL), keeping the reaction mixture below -30° C. The reaction mixture was allowed to warm to 5° C. over 3 hrs. The reaction was quenched by careful addition of water (9.0 mL). To the reaction mixture was added Solka Floc (0.25 g, 8% wt) and the mixture was stirred 20 min. The biphasic mixture was filtered over Solka Floc, then transferred to a separatory funnel where the layers were separated. The organic layer was washed with 1/2 saturated solution of NaHCO3 (2*15.0 mL) and with brine (15.0 mL) to provide 1-ethyl-1-trifluoromethyl-3-trimethylsilylprop-2-yn-1-yl 4-nitrobenzoate (TMS-acetylene ester). | |
Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone at -78 - 20℃; for 2h; | 1.4 Step 4: 3-(trifluoromethyl)pent-l-yn-3-ol; To a mixture of tϖmethylsilylacetylene (19.4 g, 198 mmol, 1 eq) in THF (500 mL, 0.396M) stirred at - 78°C under an atmosphere of nitrogen, n-butyllithium 1.6M hexanes (124 mL, 198 mmol, 1 eq) was added. The resulting mixture was stirred at -78°C forl h. Then 1 , 1 , 1 -trifluoro-2-butanone (25.0 g, 198 mmol, 1 eq) was added dropwise at -78°C and the resulting mixture was stirred at rt for 2 h. The reaction was quenched by the addition of a saturated NaHCO3 solution at 0 0C . The organic layer was separated and the aqueous phase was extracted with ether/hexane (1 : 1). The organic layers were combined, washed with brme, dried over Na2SO4. The solvent was removed by careful distillation. The crude thus obtained was re-dissolved in THF (200 mL, 1 M) under atmosphere of nitrogen at 00C, tetrabutylammonium fluoride IM THF (238 mL, 238 mmol, 1 2 eq) was added dropwise. The resulting mixture was stirred at rt for 2 h. The reaction was quenched by the addition of brme. The organic layer was separated and the aqueous phase was extracted with hexane. The organic layers were combined, washed with brme, dried over Na2SO4. The solvent was removed by careful distillation and residue was purified by distillation (collect the fraction between 100-140 0C) to afford the titled compound. 1H NMR δ (ppm)( Acetone): 5.86 (1 H, s), 3.27 (1 H, s), 1.91-1 81 (2 H, m), 1.15 (3 H, t). |
Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78 - 20℃; | ||
With n-butyllithium In tetrahydrofuran; hexane at -78℃; | 1.9 To (trimethylsilyl)acetylene (2.45 g, 25 mmol) in THF (100 mL) at -78 °C was added n- butyllithium (1.6 M in hexanes, 19 mL, 30 mmol) dropwise. After stirring for 1 hour at -78 °C, 1, 1,1- trifluoro-2-butanone (4 mL, 30 mmol) in THF (10 mL) was added dropwise, and the reaction was slowly warmed to room temperature. The mixture was diluted with Et20 (300 mL) and washed with H20, and then dried, filtered, and concentrated give the title compound. | |
Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78 - 20℃; | 1.7 Step 7: 3-Trifluoromethyl-l-trimethylsilanyl-pent-l-yn-3-ol[00339] To (trimethylsilyl)acetylene (2.45 g, 25 mmol) in THF (100 mL) at -78°C was added n- butyllithium (1.6 M in hexanes, 19 mL, 30 mmol) dropwise. After stirring for 1 hour at -78°C, 1,1, 1- trifluoro-2-butanone (4 mL, 30 mmol) in THF (10 mL) was added dropwise, and the reaction was slowly allowed to warm to room temperature. The mixture was diluted with Et20 (300 mL) and washed with H20, then dried, filtered, and concentrated to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50 %Spectr. | In tetrahydrofuran at 20℃; for 1h; | 27.1 Step 1: 3-(trifluoromethyl)hex-4-yn-3-ol Step 1: 3-(trifluoromethyl)hex-4-yn-3-ol To ethyl trifluoromethyl ketone (5.00 g, 40.0 mmol) in THF (20 ml) at room temperature was added 1-propynyl magnesium bromide (0.5 M in THF, 60 mL, 30.0 mmol). The reaction mixture was allowed to stand at rt 1 h, and concentrated in vacuo. The residue was partitioned between Et2O and aq. NH4OAc, the phases were separated, and the organic phase washed with brine, dried over MgSO4, filtered and concentrated (not to complete dryness), to afford a 50 wt. % solution (estimated by 1H NMR) of the title compound (remainder THF and Et2O), which was used without further purification. 1H NMR (400 MHz, DMSO-d6): 6.63 (s, 1H), 1.87 (s, 3H), 1.75-1.63 (m, 2H), 1.04 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: ethyl trifluoroacetate,; ethylmagnesium bromide In diethyl ether at -78℃; for 1h; Stage #2: With hydrogenchloride In diethyl ether; water | 4.1 Step 1:To a solution of ethyl magnesium bromide in diethyl ether prepared from 18.4 g of bromoethane, 4.3 g of magnesium and 150 ml of diethyl ether was added dropwise 20 g of ethyl trifluoroacetate under cooling at -78°C. The mixture was stirred at the same temperature for 1 hour, and then warmed to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid, and then extracted with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate and then filtered to obtain a solution of 1, 1, l-trifluoro-2-butanone in diethyl ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at 0℃; for 1h; | 4.2 Step 2: To a suspension of 5.6 g of sodium hydride (60% in oil) in 500 ml of tetrahydrofuran was added dropwise 31.6 g of ethyl diethylphosphonoacetate under ice-cooling. After the mixture was stirred at the same temperature for 10 minutes, the a solution of 1, 1, 1-trifluoro-2-butanone in diethyl ether obtained in Step 1 was added dropwise thereto, The mixture was stirred at the same temperature for 1 hour, and then warmed to nearly room temperature. To the reaction mixture was added 10% hydrochloric acid, and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain crude ethyl 3- trifluoromethyl-2-pentenoate . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride In ethanol; water at 80℃; for 18h; | 126 Example 126 9-Chloro-1-methyl-3-(2,2,2-trifluoro-ethyl)-2-trifluoromethyl-3,6-dihydro-pyrrolo[3,2-f]quinolin-7-one; Compound 229, Structure 12 of Scheme II, where RA=chloro, R1=methyl, R3=trifluoromethyl, R5=2,2,2-trifluoroethylTo a mixture of compound 7 (RA=chloro, RB=2-propyl) in trifluoroacetic acid at 0° C. was added trifluoroacetaldehyde ethyl hemiacetal, followed by NaBH4. After 2.5 hrs the reaction mixture was poured into ice/water. Solid was filtered and washed with water, then dried. Compound 8 (RA=chloro, R5=2,2,2-trifluoroethyl, RB=2-propyl) was obtained as a yellow solid. To a mixture of compound 8 and sodium nitrite in DMF at 0° C. was added slowly 2N HCl. After 30 min., water was added. Solid was filtered and washed with water. Compound 9 (RA=chloro, R5=2,2,2-trifluoroethyl, RB=2-propyl) was obtained as a white solid. To a mixture of compound 9 in dry THF at 0° C. was added slowly lithium aluminumhydride (1.0 M in THF). That reaction mixture was then stirred at room temperature for 1 hour. EtOAc was added slowly at 0° C. The mixture was filtered through celite. After removal of solvent, crude compound 10 (RA=chloro, R5=2,2,2-trifluoroethyl, RB=2-propyl) was used directly in the next step without further purification.Compound 10, 1,1,1-trifluoro-2-butanone, EtOH and conc. HCl were heated at 80° C. in a sealed tube for 18 hrs. The mixture was then poured into water. Solid was filtered and purified by chromatography. Compound 229 was obtained as a white solid. 1H NMR (500 MHz, acetone-d6) 11.13 (s, 1H), 8.08 (d, J=9.1 Hz, 1H), 7.58 (d, J=9.1 Hz, 1H), 6.78 (s, 1H), 5.35 (q, J=8.5 Hz, 2H), 2.70 (q, J=2.6 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | With copper(II) bis(trifluoromethanesulfonate) In N,N-dimethyl-formamide at 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With (R)-(5-(3-(3,5-bis-(trifluoromethyl)phenyl)ureido)-6-methoxyquinolin-4-yl)(8-ethylquinuclidin-2-yl)methyl 3,5-bis-(trifluoromethyl)phenylcarbamate In tert-butyl methyl ether at -30℃; for 72h; Inert atmosphere; optical yield given as %ee; | |
67% | With (1R)-(6-hydroxyquinolin-4-yl)(8-vinylquinuclidin-2-yl)methyl 3,5-di(trifluoromethyl)benzoate In dichloromethane at -78 - -25℃; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With zirconium(IV) tert-butoxide; (R)-3,3'-dibromo-1,1'-bi-2-naphthol In benzene at 20℃; for 1.2h; Inert atmosphere; optical yield given as %ee; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In diethyl ether at 0 - 20℃; | 1B Example 1B A solution of 70.0 g (201 mmol) carbethoxymethylene triphenylphosphorane in 300 mL diethyl ether was cooled to 0° C. and 25.0 g (198 mmol) 1,1,1-trifluorobutanone were added. The solution was warmed to room temperature and stirred over night. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by vacuum distillation (170 mbar and 130° C. bath temperature, main fraction: 95-96° C.). 29.0 g (75%) of the product were obtained as an oil.HPLC-MS (M1): Rt=1.77 minMS (ESI pos): m/z=196 (M+H)+ |
75% | In diethyl ether at 0 - 20℃; | 1A A solution of 70 g (201 mmol) carbethoxymethylene triphenylphosphorane in 300 ml_ diethyl ether was cooled to 00C and 25 g (198 mmol) 1.,1 ,1 -thfluorobutanone was added. The solution was warmed to room temperature and stirred over night. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure (700 mbar and 400C bath temperature). The residue was purified by vacuum distillation (170 mbar and 1300C bath temperature, main fraction: 95-96°C). 29 g (75 %) of the product were obtained as colourless oil.HPLC-MS (Method 1 ): Rt: 1.77 min. + MS (ESI pos): m/z = 196 (M+H)4 |
In dichloromethane at 0℃; for 0.25h; | F.1 [00191] Step 1 : A solution of ethyl 2-(triphenylphosphoranylidene)acetate (15 g, 44 mmol) in dichloromethane (26 mL, 40 mmol) was cooled to 0 °C and treated with 1,1,1- trifluorobutan-2-one (5 g, 40 mmol). The mixture was stirred at 0 °C for 15 minutes. The reaction mixture was concentrated in vacuo (water bath below 10 °C and vacuum at 170 Torr). With concentration Ph3PO started to precipitate out. The solids were filtered off washing with Et20. The filtrate collected was treated with Et20 (20 mL), and the solids formed were decanted off. The liquid isolated was subjected to fractional distillation (oil bath at 45-50 °C vacuum at 300 Torr) to provide a mixture of E and Z isomers of ethyl 3- (trifluoromethyl)pent-2-enoate. lH NMR (400 MHz, CDC13) δ 6.269 (s, 1H), 4.23 (q, J=7.027 Hz, 2H), 2.72-2.663 (m, 2H), 1.317 (t, J=7.027, 3H), 1.208 (t, J=7.027 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.25h; Stage #2: 2-mercaptothiazole In tetrahydrofuran for 0.0833333h; Stage #3: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 3h; | 1.2 Step 2: l.l.l-trifluoro-2-(2-mercapto-L3-thiazol-5-vDbutan-2-ol To a solution of diisopropylamine (4.32g, 42.6 mmol) in 50 ml of THF at -78 °C wasadded BuLi (1.6 M in hexanes, 26.6 ml, 42.6 mmol). After 15 min, a solution of 2-mercaptothiazole (2.0g, 17.0 mmol) in 10 ml of THF was added dropwise. After 5 min, l,l,l-trifluoro-2-butanone (1.07 g, 8.5mmol) was added. The mixture was stirred 3 h at -78 °C and partitioned between aqueous NHiCl andEtOAc. The layers were separated and the aqueous phase was extracted with EtOAc. The combinedorganic layers were dried over anhydrous MgSO4. The solvent was evaporated and the residuechromatographed on silica gel (hexanes: EtOAc; 1:1) to give the title compound. | |
With lithium diisopropyl amide In tetrahydrofuran at -78℃; | ||
Stage #1: 2-mercaptothiazole With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.166667h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 6h; Stage #3: With water; ammonium chloride In tetrahydrofuran at 20℃; | 10.A.1 Step 1: 1,1,1-Trifluoro-2-(2-mercapto-thiazol-5-yl)-butan-2-ol (10b) iPr2NH (2.0 g, 19.9 mmol) was dissolved in THF (23 mL) and cooled to -78° C. n-Butyllithium (2.5M, 8.0 mL, 19.9 mmol) was added dropwise, followed by thiazole-2-thiol (0.9 g, 7.9 mmol) in THF (5 mL). After 10 minutes, trifluoro-2-butanone (0.5 g, 4.0 mmol) was added and the reaction was stirred at -78° C. for 6 hours. The reaction was warmed to room temperature and quenched with 5% aqueous NH4Cl (20 mL). The aqueous layer was acidified and extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (50% EtOAc in hexanes) to give the desired product, 10b. |
Stage #1: 2-mercaptothiazole With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 0.583333h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 6h; | 15.1 Diisopropylamine (2.01 g, 19.9 mmol) was dissolved in THF (23 mL) and cooled to -78 °C. n-Butyllithium (2.5 M in THF, 7.96 mL, 19.9 mmol) was slowly added and the reaction stirred for 15 minutes. 2-Mercaptothiazole (0.948 g, 7.93 mmol) in THF (5 mL) was added over 10 minutes. After stirring for 10 minutes, 1 , 1 , 1 -trifluoro-butan-2-one (0.5 g, 3.97 mmol) was added. After stirring at -78 °C for 6 hours, the reaction was allowed to warm to room temperature and submitted to standard aqueous workup. The residue was purified via silica gel chromatography (0-50% EtOAc in hexanes) to yield the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: isocyanoacetic acid methyl ester With sodium t-butanolate In tetrahydrofuran at -60 - -35℃; for 1.08333h; Inert atmosphere; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -45 - 25℃; for 2.41667h; Inert atmosphere; Stage #3: With hydrogenchloride; water In tetrahydrofuran for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1.4-dibromobenzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.25h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78℃; for 0.25h; | 8.1 To a solution of 1,4-dibromobenzene (2.5 g, 10.6 mmol) in THF (50 mL) at -78° C. was added n-BuLi (6.5 mL, 10 mmol; 1.6 M in hexanes) and the mixture was stirred at -78° C. for 15 min. 1,1,1-Trifluoro-2-butanone (1.3 g, 10 mmol) was then added. After further stirring for 15 min., the mixture was quenched with aqueous NH4Cl and extracted with Ethyl acetate. Purification by combi-flash chromatography (40 g column; eluted with hexanes-Ethyl acetate (10% -20%) in 20 min.; flow rate: 35 mL/min and collected 18 mL/fraction) to yield the title compound as a colorless liquid. 1H NMR (CD3COCD3) δ (ppm): 7.58 (m, 5H), 5.52 (s, 1H), 2.28 (m, 1H), 2.10 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1,1,1-trifluoro-2-butanone With (-)-diisopinocamphenylborane chloride at 20℃; for 10h; Inert atmosphere; Stage #2: With acetaldehyde In diethyl ether at 0 - 20℃; for 24h; Inert atmosphere; Stage #3: With sodium hydroxide In diethyl ether; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23% | With acetic acid In chloroform Reflux; | |
Stage #1: 1,1,1-trifluoro-2-butanone; p-nitrobenzylamine In chloroform at 0 - 20℃; for 0.333333h; Inert atmosphere; Molecular sieve; Stage #2: With acetic acid In chloroform for 3h; Inert atmosphere; Reflux; | 2 Alkyl Trifluoromethyl Imines 1B-1F: General procedure: Under N2, to a flask charged with 4-NO2PhCH2NH2 (2.00 g, 13.0 mmol) and 4 MS (3.0 g) was added CHCl3 (20 mL). The corresponding trifluoromethyl ketone (10.0 mmol) was then added in one portion. The suspension was stirred at room temperature for 20 mins. HOAc (16.0 mmol) was added dropwise. Next the white suspension was moved to a 70° C. oil bath and refluxed for 3 h (1B-E) or 24 h (1F). After the suspension was cooled to room temperature, Hexanes (30 mL) was added. The suspension was filtered through a pad of deactivated silica (5 cm thick) and washed with Hexanes/Et2O=3/1 solution (100 mL). The filtrate was collected, and the solvent was removed. The residue was analyzed by 1H and 19F NMR, if lacking sufficient side products, the imine could be used directly. If not, the residue was applied to deactivated silica column chromatography (Hex/CH2Cl2=100/1 to Hex/CH2Cl2=10/1) to afford imine 1B-1F (29-75% yield). The spectral data of imines 1A-C and 1F were consistent with those reported in Wu & Deng, 2012, J. Am. Chem. Soc. 134:14334-14337. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With ytterbium(III) triflate In 1,4-dioxane at 110℃; for 12h; | General procedure for the preparation of ethyl 3, 3, 3-trifluoro-2-hydroxy-2-(quinolin-2-ylmethyl)propanoate (3a) General procedure: Quinaldine (100 mg, 0.70 mmol) and ethyl trifluoropyruvate (47 μL, 0.35 mol) were placed in a screw cap pressure tube along with 2 mL 1,4-dioxane. Ytterbium triflate (21 mg, 5 mol%) was added with constant stirring. The closed tube was then stirred at 90 ºC for 12 h. Inert reaction atmosphere is not necessary. After the reaction was completed, as indicated by TLC, the resulting reaction mixture was directly subjected to column chromatography (hexane/ethyl acetate 90:10 to 80:20) to get a white solid with 78% isolated yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With ytterbium(III) triflate In 1,4-dioxane at 110℃; for 12h; | General procedure for the preparation of ethyl 3, 3, 3-trifluoro-2-hydroxy-2-(quinolin-2-ylmethyl)propanoate (3a) General procedure: Quinaldine (100 mg, 0.70 mmol) and ethyl trifluoropyruvate (47 μL, 0.35 mol) were placed in a screw cap pressure tube along with 2 mL 1,4-dioxane. Ytterbium triflate (21 mg, 5 mol%) was added with constant stirring. The closed tube was then stirred at 90 ºC for 12 h. Inert reaction atmosphere is not necessary. After the reaction was completed, as indicated by TLC, the resulting reaction mixture was directly subjected to column chromatography (hexane/ethyl acetate 90:10 to 80:20) to get a white solid with 78% isolated yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With ytterbium(III) triflate In 1,4-dioxane at 110℃; for 12h; | General procedure for the preparation of ethyl 3, 3, 3-trifluoro-2-hydroxy-2-(quinolin-2-ylmethyl)propanoate (3a) General procedure: Quinaldine (100 mg, 0.70 mmol) and ethyl trifluoropyruvate (47 μL, 0.35 mol) were placed in a screw cap pressure tube along with 2 mL 1,4-dioxane. Ytterbium triflate (21 mg, 5 mol%) was added with constant stirring. The closed tube was then stirred at 90 ºC for 12 h. Inert reaction atmosphere is not necessary. After the reaction was completed, as indicated by TLC, the resulting reaction mixture was directly subjected to column chromatography (hexane/ethyl acetate 90:10 to 80:20) to get a white solid with 78% isolated yield. |
46% | With indium(III) chloride In <i>tert</i>-butyl alcohol at 60℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 65% 2: 6% | In hexane at 20℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium azide; zinc(II) chloride In water at 80℃; for 3h; | 3.2 1.1. l-Trifluoro-2-f2H-tetrazol-5-vnbutan-2-ol (3-3 To l,l,l-trifluorobutan-2-one (5.0 g, 39.7 mmol, 1.0 equiv) was slowly addedtrimethylsilylcyanide (4.7 g, 47.6 mmol, 1.2 equiv) and the resulting mixture stirred overnight at ambient temperature. To the resulting mixture was added water (80 mL) followed by zinc chloride (5.4 g, 39.7 mmol, 1.0 equiv) and sodium azide (3.1 g, 47.1 mmol, 1.2 equiv) and the mixture was heated at 80°C for three hours. The mixture was cooled to room temperature and the precipitate was filtered and dried in vacuo to afford l,l,l-trifluoro-2-(2H-tetrazol-5-yl)butan-2-ol (3-3) as a white solid. LRMS m/z (M+H)+197.0 found, 197.1 required. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With montmorillonite K10 In toluene at 130℃; for 4.5h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: 1,1,1-trifluoro-2-butanone; (R)-2-methylpropane-2-sulfinamide With titanium(IV) isopropylate In hexane; toluene at 20℃; for 12h; Inert atmosphere; Stage #2: phosphonic acid diethyl ester In hexane; toluene at -40℃; Inert atmosphere; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | In methanol at 60℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; sulfur at 120 - 150℃; for 0.5h; Microwave irradiation; Inert atmosphere; | A.A6 Method A6: One-pot Gewald reaction using microwave conditions General procedure: Method A6: One-pot Gewald reaction using microwave conditions To the solution of the aldehyde or keton (1 mmol) in EtOH (1.5 mL) the heterocyclic acetonitrile derivative (1 mmol), sulfur (1 mmol) and N-methylmorpholine (1 mmol) are added, the reaction mixture heated in a microwave oven at 120-150 °C for 30 min. and then poured on 30 mL 10% aqueous NaHC03 solution and 30 mL EtOAc and the layers are separated. The aqueous layer is extracted a second time with 30 mL EtOAc. The organic layers are washed with 30 mL brine, dried over MgS04, filtered and evaporated. The compound is purified by silica gel chromatography on a 20 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of w-heptane : EtOAc. | |
With 4-methyl-morpholine; sulfur In ethanol at 120 - 150℃; for 0.5h; Microwave irradiation; Inert atmosphere; | A6 Method A6: One-Pot Gewald Reaction Using Microwave Conditions General procedure: Method A6: One-Pot Gewald Reaction Using Microwave Conditions [0295] To the solution of the aldehyde or keton (1 mmol) in EtOH (1.5 mL) the heterocyclic acetonitrile derivative (1 mmol), sulfur (1 mmol) and N-methylmorpholine (1 mmol) are added, the reaction mixture heated in a microwave oven at 120-150° C. for 30 min. and then poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc and the layers are separated. The aqueous layer is extracted a second time with 30 mL EtOAc. The organic layers are washed with 30 mL brine, dried over MgSO4, filtered and evaporated. The compound is purified by silica gel chromatography on a 20 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 89 %Spectr. 2: 97% | Stage #1: ethyl trifluoroacetate, With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 1-phenyl-propan-1-one In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Schlenk technique; Reflux; Stage #3: With hydrogenchloride In tetrahydrofuran; water at 0℃; for 0.25h; Inert atmosphere; Schlenk technique; | General procedure for ‘trifluoroacetic ester/ketone metathesis’ and the preparation of TFMKs General procedure: Under Ar atmosphere in a dry Schlenk tube, a mixture of NaH (6.0 mmol) and trifluoroacetate (6.0 mmol) was stirred in THF (5 mL) at room temperature for 10 min. To this mixture enolizable ketones (5.0 mmol) in THF (5 mL) was added dropwise at 0 °C under Ar atmosphere. After stirring for 2-6 h at reaction temperature, the reaction solution was cooled to 0 °C again and quenched with 6 mL of 1 mol/L HCl. After stirring for additional 15 min, the mixture was neutralized with saturated NaHCO3 solution. After usual workup, the residue was purified by chromatography on silica gel to afford the trifluoromethyl alkyl ketone products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In tetrahydrofuran; at 0 - 20℃;Large scale; | General procedure: A mixture of the above <strong>[104863-67-4]2,2,2-trifluoro-N-methoxy-N-methylacetamide</strong> (3 Kg, 90 % purity, 0.017 kmol) in anhydrous THF (30 L) was cooled to 0 C and treated with 0.5 M Grignard reagent in THF (42 L). The reaction mixture was stirred at 0 C for 0.5 h and allowed to warm to room temperature. The resulting mixture was stirred at room temperature overnight. The reaction was quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate three times. The organic layers were combined and washed with water and brine, dried over MgSO4 and filtered. After rectification, the resulting α-trifluoromethylated ketones were obtained (95 % purity, 90 % yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In toluene at 0℃; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
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With amine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With titanium tetrachloride In diethyl ether for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With titanium tetrachloride In diethyl ether for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With C28H28N2O4S4; water; palladium diacetate; potassium trifluoroacetate; trifluoroacetic acid In 1,4-dioxane at 80℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With magnesium sulfate In toluene at 20℃; for 24h; Inert atmosphere; | 2-(1H-Pyrrol-2-yl)-N-(1,1,1-trifluorobutan-2-ylidene)aniline, 34: A slurry of pyrroloaniline 1 (100 mg, 0.63 mmol), 1,1,1-trifluorobutanone (0.43 mL,3.17 mmol) and oven dried anhydrous magnesium sulfate (380 mg, 3.16 mmol) in anhydroustoluene (20 mL) was stirred at room temperature for 24 hours. At this point TLC (1:4 diethylether/petrol 40-60) showed formation of no new products. 1,1,1-trifluorobutanone (0.86 mL,6.3 mmol) and oven dried anhydrous magnesium sulfate (761 mg, 6.32 mmol) were addedand the resulting slurry was heated to 50 oC in a sealed vial for 20 hours, cooled to roomtemperature and then filtered through a plug of Celite washing with anhydrous diethyl ether.The filtrate was concentrated under reduced pressure. Purification of the residue via columnchromatography eluting with 1:19 diethyl ether/petrol 40-60 afforded the title compound 34as a yellow oil (103 mg, 61 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1R,2R)-2-(pyrrolidin-1-yl)cyclohexyl)thiourea; sodium phosphate at -10℃; for 61h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With glacial acetic acid for 12h; Reflux; | |
In toluene at 110℃; for 18h; | Step 1: A'-(Ll.l-Trifluorobutan-2-ylidene)benzohydrazide To a solution of 1,1,1 - trifluorobutan-2-one (1.39 g, 11.0 mmol) in toluene (10 mL) was added benzohydrazide (1.50 g, 11.0 mmol), and the reaction mixture was heated to 110 °C for 18 h. The reaction was cooled to rt, poured into water and then filtered. The solid was washed with water and further dried to give the desired crude title compound. LCMS [M+H]+= 245.4 (calcd. 245.1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.3% | With trifluoroacetic acid In trifluoroacetic acid for 18h; Reflux; | Intermediate 109A: 4-Bromo-5-fluoro-3-methyl-2-(trifluoromethyl)-1H-indole-7-carboxylic acid A mixture of 4-bromo-5-fluoro-2-hydrazinylbenzoic acid, HCl (5.0 g, 17.51 mmol), and 1,1,1-trifluoro-2-butanone (6.62 g, 52.5 mmol) in TFA (8.0 mL) was stirred at reflux for 18 hr. The mixture was concentrated. The crude product was added to DCM and the precipitate was collected by filtration and dried under high vacuum. Yield was 4-bromo-5-fluoro-3-methyl-2-(trifluoromethyl)-1H-indole-7-carboxylic acid (3.86 g, 10.22 mmol, 58.3% yield) as white solid. 1H NMR (400 MHz, methanol-d4) δ 7.75 (d, J=9.3 Hz, 1H), 2.69 (q, J=1.7 Hz, 3H). LCMS: 1.07 min, M+H product not ionize. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | Stage #1: 6-amino-4-(trifluoromethyl)quinoline-2-(1H)-one; 1,1,1-trifluoro-2-butanone With trifluoroacetic acid at 20℃; for 1h; Stage #2: With sodium tetrahydroborate at 20℃; for 16h; | 25 preparation of 6-((1,1,1-trifluorobutane-2-yl)amino)-4-(trifluoromethyl)quinolin-2(1H)-one 1 g (4.38 mmol) of 6-amino-4- (trifluoromethyl) quinolin-2 (1H) -one was added to a 100 ml flask and dissolved in trifluoroacetic acid and cooled to 0 ° C. 1.2 ml (2.0 eq) of 1,1,1-trifluoro-2-butanone was added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. The reaction solution was cooled to 0 ° C, NaBH 4 was slowly added thereto, and the mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, and ethyl acetate and 2N aqueous NaOH solution were added thereto and stirred. The reaction solution was separated into layers, and the aqueous layer was removed. The organic layer was separated, dried over Na2SO4, and concentrated under reduced pressure. The concentrated residue was separated by column chromatography and concentrated under reduced pressure to give 420 mg (28%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: 1-Phenyl-3-buten-1-ol With Jones reagent at 0℃; Stage #2: 1,1,1-trifluoro-2-butanone With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1R,2R)-2-(pyrrolidin-1-yl)cyclohexyl)thiourea; sodium phosphate at -10℃; for 80h; enantioselective reaction; | 3.1. General Experimental Procedure for the One-Pot Tandem Direct Asymmetric Vinylogous Aldol Reaction ofAllyl Ketones 1 to Trifluoromethyl Ketones 2 General procedure: Jones reagent (0.25 mL) was added dropwise to a solution of homoallic alcohols 1 (0.4 mmol,4.0 equiv.) in tert-butylbenzene (1.0 mL) at 0° C over a period of 3.5-7 h. When the reactionwas completed (monitored by TLC), the sample was stewed for a moment until a clear separationbetween the organic and aqueous phase was formed, and the aqueous phase was released. Thenthe trifluoromethyl ketone 2 (0.1 mmol, 1.0 equiv.) was added, the reaction mixture was stirred at10° C for 10 min. Sodium phosphate (0.2 mmol, 2.0 equiv.) and catalyst 4 (0.01 mmol, 0.1 equiv.)were added sequentially (10 min interval). The reaction mixture was stirred at 10° C and monitoredby TLC. Upon complete consumption of trifluoromethyl ketone 2, the reaction mixture was directlyloaded onto a short silica column, followed by gradient elution with PE/EA mixture (20/1-5/1 ratio).Removing the solvent in vacuum afforded products 5a-y. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With P(p-C6H4F)3 In toluene at 65℃; for 96h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With silver nitrate; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 20℃; for 24h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With n-butyllithium; diisopropylamine In diethyl ether; water at -78 - 20℃; for 1h; | 1 Synthesis of 2, 6-difluoro-3- (4-methylpyridin-2-yl) benzaldehyde (Compound A-2) The torch used in well-dried 100 mL 3-neck round bottom flask was charged withdiisopropylamine (4.7g 0.04678 mol) and the mixture was dissolved in ethyl ether andthen, at 0 ° C 2.5M n-BuLi (18.7 mL, 0.04678 mol) and the mixture stirred for 30minutes and made the LDA (Lithium diisopropylamine). Then put the 2- (2,4-difluorophenyl) -4-methyl-pyridine (compound 1-A) (8.0 g, 0.03899 mol) in anotherflask was dissolved in ethyl ether, slowly inject LDA at -78 ° C It was. Then, after 1and then the reaction was conducted at -60 ° C for a time, the rapid injection of ethyl 2,2,2-trifluoroacetate (6.6 g, 0.04678 mol) at a time, up to room temperature, 1 hourreaction, the reaction water It was terminated. After then extracted with ethyl ether,then washed twice with chlorine can, using the anhydrous MgSO4 was removedmoisture. And 1:10 ethyl acetate-hexane mixture as used in column chromatography toobtain the objective compound of the 2,6-difluoro-3 - (4-methyl-pyridin-2-yl)benzaldehyde (Compound A-2) a It was obtained (yield = 54%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In toluene at 0 - 20℃; for 0.5h; | 2.1.2.1 General procedurefor the synthesis of 2,3-dimethylquinoxaline-1,4-di-N-oxide derivatives (1-3) and2-methyl-3-trifluoromethylquinoxaline-1,4-di-N-oxide derivative (4) General procedure: Initial intermediates (1-3) were synthesized and purified asdescribed previously by our group. The appropriate benzofuroxan (BFX) (10.0 mmol) was dissolved in 1-5 mLof triethylamine (TEA), depending on the BFX used; then, the suspension wascooled (0 °C). Next, 1,5 mL of pyrrolidine was added dropwise. TEA andpyrrolidine act as both solvent and catalyst. Finally, butanone (15.0 mmol) wasadded dropwise to the pre-cooled solution. The mixture reaction was stirred atroom temperature for 30 minutes; it was then filtered and washed with coldethanol and diethyl ether. The obtained solid corresponds to the derivatives 1-3. In the case of intermediate 4 the procedure was similar. Theappropriate benzofuroxan (BFX) (12.0 mmol) was dissolved in 15 mL of toluene;then, 20 mmol of 1,1,1-trifluoro-2-butanone and 5 mL of TEA were addeddropwise. Finally, the mixture reaction was stirred at room temperature for20-30 hours. The solvent was eliminated under reduce pressure and the finalresidue was purified by column chromatography on silica gel usingtoluene/dioxane 80:20 (v/v) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | Stage #1: C10H18NO2S(1+)*ClO4(1-) With sodium hydride In acetonitrile at 0 - 20℃; for 2h; Stage #2: 1,1,1-trifluoro-2-butanone In acetonitrile for 0.75h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | Stage #1: C10H18NO2S(1+)*ClO4(1-) With sodium hydride In acetonitrile at 0 - 20℃; for 2h; Stage #2: 1,1,1-trifluoro-2-butanone In acetonitrile for 0.75h; diastereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: N,N-Dimethylcarbamoylmethyl dimethylsulfonium chloride With sodium hydride In acetonitrile at 20℃; for 2h; Stage #2: 1,1,1-trifluoro-2-butanone In acetonitrile at 20℃; for 0.75h; stereoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With 2-phenyl-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazin-2-ium tetrafluoroborate; potassium carbonate; cesium fluoride In tetrahydrofuran at 20℃; for 36h; Schlenk technique; Molecular sieve; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With C28H28N2O4S4; water; palladium diacetate; potassium trifluoroacetate; trifluoroacetic acid In 1,4-dioxane at 80℃; for 12h; Sealed tube; | 6.2 General procedure for the β-arylation with diaryliodonium salts General procedure: An 8mL vial was charged with Pd(OAc)2 (9.0mg, 0.1 equiv.), KTFA (122mg, 2.0 equiv.), Mesitylaryliodonium salt (0.4mmol), bis-sulfilimine ligand 9 (24mg, 0.1 equiv.), TFA (200μL), ketone (1.0mmol, 2.5 equiv.), H2O (100μL) and 1,4-dioxane (2mL). The vial was sealed with a PTFE lined cap (no inert atmosphere is required) and heated in a pie-block at 80°C for 12h under stirring. Then, the vial was allowed to cool to room temperature and the mixture was filtered through a small plug of silica gel, eluted with diethyl ether. The solvent was then removed in vacuo and flash column chromatography (hexane/ethyl acetate or DCM/methanol) of the residue gave the arylation product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: (E)-(4,4-dibromo-2-methylbut-1,3-dien-1-yl)benzene In tetrahydrofuran; hexane at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #3: acetic anhydride In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 2-mesityl-5,6-dihydro-8H-[1,2,4]-triazolo[3,4-c][1,4]oxazin-2-ium tetrafluoroborate; caesium carbonate In tetrahydrofuran at 25℃; for 12h; Molecular sieve; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With 1,4-diaza-bicyclo[2.2.2]octane In acetonitrile at 20℃; for 0.0833333h; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With toluene-4-sulfonic acid at 120℃; for 16h; Sealed tube; Molecular sieve; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: 1-fluoro-4-((1-(4-iodophenyl)cyclopentyl)sulfonyl)benzene With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.166667h; Inert atmosphere; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran; pentane at -78℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In 1,4-dioxane at 90℃; for 5h; Inert atmosphere; | General procedure for the deacetylation of methyl ketones. General procedure: For a 0.05-mmolscale reaction, a 1,4-dioxane (1 ml) solution of the ketone substrate (0.05 mmol,1.0 equiv.), 2-hydrazinyl-4-methylpyridine (6.4 mg, 0.052 mmol, 1.04 equiv.) and p-TsOH·H2O (stock solution in 1,4-dioxane; 0.05 M, 3.0 μl, 0.003 equiv.) was heated at 90 °C for 5 h under N2 atmosphere in an 8-ml vial. After cooling to room temperature, the vial was charged first with [Ir(cod)2]BArF (6.4 mg, 0.005 mmol,0.1 equiv.) and L1 (2.0 mg, 0.005 mmol, 0.1 equiv.) under air atmosphere, and then with 3 Å molecular sieves (pre-dried, 100 mg) and 1,3-butadiene (20 wt% in PhMe, 170 μl, about 10 equiv.) in a glovebox. The vial was sealed and heated at 160 °C while stirring for 72 h. After cooling to room temperature, the reaction mixture was filtered through Celite, concentrated under reduced pressure and further purified by flash column chromatography over silica to give the products. General procedures for the formal homologation of linear ketones and deconstructive pyrazole synthesis from cyclic ketones, together with full experimental details and characterization of new compounds, can be found in Supplementary Information. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69 %Spectr. | With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran at 20℃; for 72h; Inert atmosphere; Sealed tube; diastereoselective reaction; | 2. General experimental procedure for products 3 General procedure: To a flame dried sealing tube were added Pd(OAc)2 (2.25 mg, 0.01 mmol),(rac)-BINAP (12.45 mg, 0.02 mmol), freshly distilled anhydrous tetrahydrofuran (1.0mL). The resulting mixture was allowed to stir for 30 mins. The ketone 2 (0.2 mmol) and vinyl cyclopropane 1 (0.5 mmol) were added subsequently. The resulting reaction mixture was stirred at room temperature for 72 h. After the volatile was removed in vacuo, the ratio of two diastereoisomers was determined by crude 1H NMR. The yieldwas determined by NMR using mesitylene as the internal standard. Then the resulting residue was purified by preparative TLC to afford pure sample for characterization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: 1,1,1-trifluoro-2-butanone With dmap; (Ra)-1,1'-([1,1'-bianthracene]-2,2'-diyl)bis(3-(3,5-bis(trifluoromethyl)phenyl)thiourea) In tetrahydrofuran at -20℃; for 0.166667h; Inert atmosphere; Stage #2: nitromethane In tetrahydrofuran at -20℃; for 12h; Inert atmosphere; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium L-ascorbate In aq. phosphate buffer; ethanol at 70℃; for 18h; Sealed tube; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86 % de | Stage #1: propionic acid With B-bromodicyclohexylborane; triethylamine In diethyl ether at 0℃; for 1h; Inert atmosphere; Stage #2: 1,1,1-trifluoro-2-butanone In diethyl ether at -78 - 0℃; for 3.5h; Inert atmosphere; Overall yield = 56 percent; diastereoselective reaction; | A typical experimental procedure is as follows: General procedure: All operations were carried out in a nitrogen atmosphere. B-bromodicyclohexylborane (Chx2BBr) (4.8 mmol) was transferred to a 50 mL round-bottom flask and dissolved in anhydrous ether (30 mL) followed by dropwise addition of triethylamine (0.67 mL, 4.8 mmol) to the stirred solution at 0 °C. The acid (2.0 mmol) dissolved in 2 mL of anhydrous Et2O was then added, dropwise, to the above solution at 0 °C. The reaction mixture was stirred at 0 °C for 1 h, cooled to -78 °C, followed by the dropwise addition of the ketone (2.4 mmol). The reaction mixture was stirred for 1 h at the same temperature (-78 °C), warmed to 0 °C and stirred for 3 h. The reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate (5 mL) and stirred for 1 h at room temperature. After separation of the layers, the organic phase was treated with additional saturated aqueous sodium bicarbonate solution. The combined aqueous layers were washed with ether, acidified with 6 M HCl, saturated with NaCl, and extracted with ether (3 x 10 mL). The combined ether layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to obtain the anti-aldol products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With 5a(R),10b(S)-5a,10b-dihydro-2-(pentafluorophenyl)-4H,6H-indeno[2,1-b][1,2,4]triazolo[4,3-d][1,4]oxazinium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 6h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 29% 2: 11.1% | With ammonium nitrate; potassium chloride at 180℃; for 2h; Sealed tube; | 1; 8 NH4NO3 was also tested as an oxidant for ethane functionalization (Scheme 2). Thisserved to demonstrate the potential scope of reactivity of NH4NO3 and provided further evidence for the formation of RNO2 from RH (R = Me, Et) when nitrates were used as the oxidant. Spiking a reaction mixture with a known standard of nitroethane supported the conclusion that it was generated during the reaction. When using methane as the substrate, spiking the resultingreaction mixture with nitromethane was also consistent with the its formation. Thus, MeNO2 andEtNO2 were concluded to be functionalization products from the reactions with methane andethane, respectively. Yields relative to nitrate for ethane functionalization are higher than thoseobserved with methane under similar conditions, with -40% total yield of EtX (X = TFA, NO2)(Scheme 18). The simple nitrate oxidant is selective for the partial oxidation of both methane and ethane, indicating the ability of oxidants other than iodine oxides to be successful in the OxE reaction without deleterious effects with respect to over-oxidation. Scheme 2. Ethane functionalization under optimized conditions with KCI and NH4NO3.CH4 (300 psi), KCI (0.1 mmol), NH4NO3 (1.1 mmol), HTFA (8 mL), 180 °C, 2 h.deviations based on three experiments are shown. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 46% 2: 11% | With manganese(IV) oxide; iodine at 180℃; for 4h; | 11 Example 11: High Selectivity for Mono-Functionalized Product at High Conversion of Ethane Under further optimized reaction conditions, very high conversion of ethane to EtTFA and TFACH2CH2TFA is observed, at high selectivity for the mono-oxidized product (Scheme 18). This expands the range of selectivity and conversion of potential claims for the oxidation of other light alkanes than methane. Scheme 18. Activity of Mn02 for ethane activation in HTFA with added iodine. Yield and standard deviations are based on three experiments. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: phenylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Stage #2: 1,1,1-trifluoro-2-butanone In tetrahydrofuran at -78℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1R,2R)-2-(pyrrolidin-1-yl)cyclohexyl)thiourea at -15℃; Molecular sieve; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With chloro-trimethyl-silane; tetrabutylammomium bromide; tetraethylammonium hexafluorophosphate In acetonitrile at 20℃; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | Stage #1: ethyl 2-diazo-3-oxobutanoate With titanium tetrachloride; triethylamine In dichloromethane at -65℃; for 1h; Stage #2: 1,1,1-trifluoro-2-butanone With titanium(IV) isopropylate In dichloromethane at -65℃; for 2h; | 9.1 Step 1: To a solution of ethyl 2-diazo-3-oxo-butanoate (12 g, 76.9 mmol) in DCM (420 mL) stirring at -65 °C was added triethylamine (8.71 g, 12 mL, 86.1 mmol) and titanium tetrachloride (85 mL of 1 M, 85.0 mmol). The resulting deep red solution was stirred at -65 °C for 1 hour. A solution of 1,1,1-trifluoro-2-butanone (9.75 g, 10.5 mL, 77.4 mmol) and Ti(Oi-Pr)4 (23.1 g, 24 mL, 81.3 mmol) in DCM (100 mL) was added dropwise and the resulting mixture was stirred at -65 °C for 2 hours then allowed to warm to ambient temperature overnight. The reaction mixture was quenched with saturated NH4Cl solution (200 mL) and extracted with DCM (3 x 150 mL). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. Purification by reverse-phase flash chromatography (C18 silica, acetonitrile/water 0-70%) afforded ethyl 2-diazo-5-hydroxy-3-oxo-5-(trifluoromethyl)heptanoate (11.21 g, 51%) as a yellow liquid. 1H NMR (400 MHz, DMSO-d6) δ 5.99 (s, 1H), 4.25 (q, J = 7.1 Hz, 2H), 3.28 (d, J = 15.4 Hz, 1H), 3.16 (d, J = 15.4 Hz, 1H), 1.84 (dp, J = 25.7, 7.1 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H), 0.93 (td, J = 7.5, 1.2 Hz, 3H) ppm; 19F NMR (376 MHz, DMSO-d6) δ - 78.78 ppm. ESI-MS m/z calc.282.0827, found 282.95 (M+1)+. |
Tags: 381-88-4 synthesis path| 381-88-4 SDS| 381-88-4 COA| 381-88-4 purity| 381-88-4 application| 381-88-4 NMR| 381-88-4 COA| 381-88-4 structure
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H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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