| 95.4% |
With thionyl chloride; N,N-dimethyl-formamide In toluene for 4h; Reflux; |
1.2 (2) Preparation of o-trifluoromethylbenzoyl chloride
To a 250 mL three-necked flask, 9.50 g (0.05 mol) of o-trifluoromethylbenzoic acid, 8.95 g (0.075 mol) of thionyl chloride, 20 mL of toluene as a solvent, two drops of DMF as a catalyst, and a tail gas absorption device connected to the bottle mouth were added. , warmed to reflux, reacted for 4 h,The disappearance of the o-trifluoromethylbenzoic acid was detected by TLC, and the solvent was evaporated under reduced pressure to give 9.95 g of pale yellow liquid o-trifluoromethylbenzoyl chloride, yield 95.4%. |
|
With thionyl chloride |
|
|
With thionyl chloride |
|
|
With thionyl chloride for 0.5h; Heating; |
|
|
With thionyl chloride for 3h; Heating; |
|
|
With thionyl chloride for 12h; Heating; |
|
|
With thionyl chloride In chloroform for 1h; Heating; |
|
|
With oxalyl dichloride In dichloromethane for 2.5h; |
|
|
With thionyl chloride In toluene for 1h; Heating; |
|
|
With oxalyl dichloride In dichloromethane at 20℃; for 4h; |
1.A
EXAMPLES; Example 1; (+/-)-cis-6-(Trifluoromethyl)-2,3,3a,4-tetrahydro-1H-pyrrolo[3,4-c]isoquinolin-5(9bH)-one hydrochloride; Part A. N,N-Diethyl-2-(trifluoromethyl)benzamide; To a solution of 2-trifluoromethylbenzoic acid (20.0 g, 105 mmol) in 500 mL of methylene chloride was added oxalyl chloride (18.4 mL, 210 mmol) followed by 8 drops of DMF. The reaction was allowed to stir at ambient temperature for 4 h and then was concentrated in vacuo to a solid. The solid was taken up in 500 mL of methylene chloride and then there was added diethylamine (24 mL, 231 mmol) dropwise as a solution in 50 mL of methylene chloride. The resulting mixture was allowed to stir at ambient temperature for 18 h. The reaction was concentrated in vacuo. The residue was diluted with EtOAc, washed sequentially with 1N HCl, sat'd. aq. NaHCO3 and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated to afford 22 g (85%) of the title compound as an oil. 1H NMR (CDCl3): δ 7.68 (d, 1H, J=7.7 Hz), 7.57 (t, 1H, J=7.4 Hz), 7.49 (t, 1H, J=7.7 Hz), 7.32 (d, 1H, J=7.1 Hz), 3.90-3.82 (m, 2H), 3.29-3.22 (m, 2H), 1.23 (t, 3H, J=7.2 Hz), 1.03 (t, 3H, J=7.2 Hz). LRMS (ESI): 246.12 (M+H)+. |
|
In thionyl chloride |
R.9 2-(Trifluoromethyl)benzoyl chloride
Reference Example 9 2-(Trifluoromethyl)benzoyl chloride A solution of 2.0 g of o-trifluoromethylbenzoic acid in 21 ml of thionyl chloride is heated at reflux for 1 hour. The volatiles are evaporated in vacuo to give a residue which is concentrated from toluene three times and dried under vacuum to give 2.1 g of the desired product as a residue. |
|
In thionyl chloride |
R.9 2-(Trifluoromethyl)benzoyl chloride
REFERENCE EXAMPLE 9 2-(Trifluoromethyl)benzoyl chloride A solution of 2.0 g of o-trifluoromethylbenzoic acid in 21 ml of thionyl chloride is heated at reflux for 1 hour. The volatiles are evaporated in vacuo to give a residue which is concentrated from toluene three times and dried under vacuum to give 2.1 g of the desired product as a residue. |
|
With thionyl chloride In chloroform at 20℃; for 1.25h; Heating / reflux; |
5.I
In the first instance, trifluoro methyl benzoyl chloride which is used as one of the starting material is prepared as follows:Thionyl chloride (62.4 g, 0.53mol) is added over a period of 15 min to a solution of 2- trifluoro methyl benzoic acid (Aldrich) (20.0 g, 0.106mol) in chloroform (200ml) at room temperature. -The reaction mixture is heated to reflux temperature for 1 hour. The excess of thionyl chloride is removed by co-distillation with chloroform under reduced pressure at 40° C. After the end of the distillation, the resulting trifluoro methyl benzoyl chloride is cooled down to room temperature and dissolved in 100 ml chloroform. A solution of 4-methyl-3-nitroaniline (9.80 g, 0.06mol) in chloroform (120 ml) is cooled to -5° C and triethyl amine (32.2 g, 0.32mol) of is added. Trifluoromethyl benzoyl chloride in chloroform prepared as described above is added drop wise at -5° C over a period of 30-45 min. The resulting suspension is stirred for 1 hr at -5° C. The suspension is distilled to a residual volume of 150 ml and filtered, washed with chilled chloroform and dried in vacuum to give 19.0 g of novel (2-trifluoromethyl) -N - (4-methyl-3-nitr6-phenyl)-benzamide of the formula (XDI) where R represents methyl, X represents CH and n=l (92%) as pale yellow crystals (97.50% purity by HPLC) MR-120-130°C |
|
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 45℃; for 5h; |
|
|
With thionyl chloride In dichloromethane for 3h; Heating; |
|
|
With oxalyl dichloride In dichloromethane at 20℃; |
63
2-Trifluoromethyl benzoic acid (1 g, 5.26 mmols) was dissolved in dichloromethane (15 ml_). Oxalyl dichloride (1.67 g, 13.15 mmols) was added dropwise and stirred for 2 hours at room temperature. The reaction mixture was concentrated under reduced pressure to give 2-trifluoromethyl benzoyl chloride as a crude intermediate (1.1 g). [(4-{4-methyl-5-[2- (trifluoromethyl)phenyl]-4H-1 ^^-triazol-S-ylJbicycloP^^Joct-i-y^methylJamine (50 mg, 0.13 mmol) was dissolved in dichloromethane (3 ml.) and triethylamine (0.075 ml_, 0.54 mmol) was added. The crude 2-trifluoromethyl benzoyl chloride (57 mg, 0.27 mmol) was added to the solution and the reaction was stirred for 2 hours at room temperature. The reaction was diluted with water and extracted with dichloromethane (3 x 5 ml_). The combined organic layers were dried with magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by HPLC (Sepax 21.2 mm x 250 mm column, 10-80% MeCN/H2O (with 0.07% TFA) over 21 min) to give the title compound as a white solid.(44 mg, 0.08 mmol, 60% yield).LCMS - RT = 1.86 min, M/Z (M+H) = 5371H NMR (400 MHz. DMSOd6) δ ppm 7.99 (m, 1 H), 7.88 (m, 2 H), 7.79 (m, 1 H), 7.69 (m,2 H), 7.62 (m, 1 H), 7.54 (d, 1 H), 3.63 (s, 3 H), 3.21 (s, 2 H), 2.15 (m, 6 H), 1.72 (m, 6 H). |
|
With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran for 1h; Inert atmosphere; |
|
|
at 0 - 20℃; Inert atmosphere; |
|
|
With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 4 - 20℃; for 1.5h; |
|
| 700 mg |
With thionyl chloride Reflux; |
|
|
With thionyl chloride In N,N-dimethyl-formamide; toluene at 20℃; Inert atmosphere; |
4.2. General procedure for the preparation of a solution of acid chlorides in CH2Cl2
General procedure: To a solution of carboxylic acids (1.7 mmol) in dry DMF (100 μL) and dry toluene (15 mL) under nitrogen atmosphere, freshly distillated thionyl chloride (3.4 mmol) was added and the solution was stirred at room temperature overnight. The solvent and thionyl chloride were removed under vacuum. The acid chloride was dissolved with dichloromethane (15 mL) under nitrogen atmosphere and directly used for the synthesis of the boronic acid. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; |
|
|
With oxalyl dichloride In dichloromethane at 20℃; for 2h; |
|
|
With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 60℃; for 5h; Inert atmosphere; |
|
|
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere; |
|
|
With thionyl chloride at 85℃; for 0.5h; Reflux; |
|
|
With thionyl chloride; N,N-dimethyl-formamide for 5h; Reflux; |
|
| 18.1 g |
With thionyl chloride In 1,2-dichloro-ethane Reflux; |
1
2-trifluoromethylbenzoyl chloride, To a mixture of 2-trifluoromethylbenzoic acid (0.1 mol) and 1,2-dichloroethane (150 mL) at room temperature thionyl chloride (0.13 mol ) was added, After the dropping completed, heated to reflux reaction for 3 ~ 6hr. After cooling, the solvent and the excess amount of thionyl chloride were distilled off under reduced pressure to give 18.1 g of the title compound as a pale yellow liquid. |
|
With thionyl chloride In toluene for 2h; Reflux; |
4.1. General procedure for morpholine amides
General procedure: To the carboxylic acid (4.98 mmol), PhMe (25 mL) was added followed by SOCl2 (1.1 mL, 14.92 mmol). The suspension was heated to reflux for 2 h before the solvent was removed under reduced pressure. The mixture was dissolved in dry DCM (10 mL) before K2CO3 (1.5 g, 10.85 mmol) was added and morpholine amine (1.5 mL) was added drop wise at 0 °C. The cooling bath was removed after 30 min and stirring was continued at rt overnight. The mixture was filtered, the solvent evaporated and the crude material was purified by column chromatography. |
|
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 16h; Inert atmosphere; |
|
|
With thionyl chloride at 0℃; for 2.5h; Inert atmosphere; Reflux; |
|
|
With thionyl chloride In N,N-dimethyl-formamide at 20℃; for 2h; Reflux; |
1.6
15 mL of thionyl chloride was added to a solution of 0. 57 g (0.003 mol) O-trifluoromethylbenzoic acid in a reaction flask, A solution of N, N-dimethylformamide was added dropwise at room temperature with stirring, The reaction was warmed to the reflux reaction. After 2 hours, the excess amount of thionyl chloride was removed under reduced pressure, 5 mL of dichloromethane was added, This was added dropwise to a solution of 0. 40 g (0.002 mol) of 2-chloro-5, 6,7,8-tetrahydro-1,6-naphthyridine hydrochloride and 0. 41 g (0.004 mol) Triethylamine in 20 mL of dichloromethane at room temperature for 3 hours, The reaction solution was washed with 50 mL of saturated brine and the organic phase was dried over anhydrous magnesium sulfate and distilled under reduced pressure. The residue was subjected to column chromatography (ethyl acetate: petroleum ether = 1: 5 to 1: 2) to give a white Solid 0.44 g, m.p. 109.5. |
|
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane for 4h; Cooling; Reflux; |
|
|
With thionyl chloride In 1,2-dichloro-ethane at 20℃; Reflux; |
|
|
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 55℃; for 5h; |
|
|
In thionyl chloride |
90 2-(Trifluoromethyl)benzoyl chloride
EXAMPLE 90 2-(Trifluoromethyl)benzoyl chloride A solution of 2.0 g of o-trifluoromethylbenzoic acid in 21 ml of thionyl chloride is heated at reflux for 1 hour. The volatiles are evaporated in vacuo to give a residue which is concentrated from toluene three times and dried under vacuum to give 2.1 g of the desired product as a residue. |
|
Stage #1: 2-trifluoromethylbenzoic acid With N,N-dimethyl-formamide In dichloromethane at 0℃; for 0.0833333h;
Stage #2: With phosgene In dichloromethane at 20℃; for 12h; |
|
|
With thionyl chloride at 79℃; for 6h; |
1.1-5.1 A method for synthesizing fluopyram, comprising the following steps:
In step 1, 96 g of o-trifluoromethylbenzoic acid and 200 g of thionyl chloride were added to a 500 mL three-necked flask, stirring was started at a rotation speed of 95 rpm, and the temperature was raised to 79 ° C and refluxed for 6 hours, followed by a vacuum degree of -0.085MPa,The sulfoxide is recovered under vacuum at a temperature of 55 ° C for 1.5 hours to obtain o-trifluoromethylbenzoyl chloride, hydrogen chloride and sulfur dioxide gas; the specific chlorination process is as shown in formula (1): |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 5h; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; |
|
|
With oxalyl dichloride |
|
|
With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5h; |
|
|
Stage #1: 2-trifluoromethylbenzoic acid With N,N-dimethyl-formamide In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere;
Stage #2: With oxalyl dichloride In dichloromethane Inert atmosphere; |
|
|
With thionyl chloride |
|
|
With oxalyl dichloride at 0 - 20℃; |
2.1 General procedure for the preparation of benzamides 1a-1ac 1-2
General procedure: Acid chloride (20 mol) was prepared from the corresponding carboxylic acid and oxalyl chloride. Acid chloride was added to a solution of 2,3,4,5,6-pentafluoroaniline (22 mmol) in toluene (50 mL). The reaction mixture was stirred for 24 h under reflux. After cooling to room temperature, the precipitate was filtered off, washed with water, and recrystallized from toluene or ethyl acetate/hexane to give the products 1 (the crude mixture was sometimes purified by flash chromatography if necessary). |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; |
|
|
With oxalyl dichloride In dichloromethane |
|
|
With thionyl chloride at 50℃; for 2h; |
|
| 175.0 g |
With thionyl chloride at 80 - 85℃; |
1-4
Add 157.8g (0.83mol) o-trifluoromethylbenzoic acid, 940g 1,2-dichloroethane into a mechanical stirring, condenser,In a 2000ml three-necked flask with a thermometer, drop 108.6g (0.91mol) of thionyl chloride within 30 minutes, and react at 80 - 85 °C for 2 - 3 hours.The end point of the reaction was determined according to the analysis result of liquid chromatography. After the reaction was completed, the reaction solution was desolventized under negative pressure to obtain 175.0 g of brown oily o-trifluoromethylbenzoyl chloride, and proceed to the next step. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; for 4.5h; Inert atmosphere; |
|
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
Life Science
HazMat Fee +
For Research Only
100K+ Compounds
Competitive Price
1-2 Day Shipping
