2-Bromo-5-fluorobenzotrifluoride

Colorless liquid

A 1 L stainless steel reactor was cooled to -10 ° C, Followed by adding to the kettle 450 g anhydrous hydrofluoric acid, 6.0g anhydrous potassium fluoride, 248 g of the last step of the amino material, and then 75.5 g of sodium nitrite in the batch slowly added to the reaction system, and the reaction system temperature does not exceed 5 , After stirring, the mixture was stirred for 30 min to complete the diazotization reaction. The temperature was raised to 60 ° C and maintained at this temperature. The fluorinated diazonium salt began to decompose slowly and evolve, and the exhaust gas was absorbed by the lye after passing through a cooling buffer. Reaction does not release the gas after the end of the reaction, The excess hydrofluoric acid in the kettle is recovered and cooled to 0 ° C, To the kettle was added 10percent KOH solution neutral to neutral, Steam distillation of colorless liquid 2-bromo-5-fluorotrifluorotoluene crude 233 g, Distilled rectification by packed distillation column, collecting 110 ° C-120 ° C fraction at 40 mmHg to obtain colorless transparent liquid 209 g, 2-bromo-5-fluorotrifluorotoluene product, GC content: 99percent, yield: 86.8percent.General procedure: A mass percentage of 30percent hydrochloric acid 1125 g was added to the four-necked flask (the mass percentage was the percentage of the total mass of the hydrochloric acid in the total amount of hydrochloric acid), 1125 g of water, A solution of 3-trifluoromethyl-4-bromoaniline was added dropwise at 25 ° C (about 750 g)Dropping time for 0.5 ~ 1.5h, after the drop of insulation 3h, then cooled to 0 ° C, in part by adding solid sodium nitrite 213g, Feeding time for 2 ~ 10h, feeding 0.5h after the completion of sampling, Starch Potassium Iodide Test Paper Check whether diazotization is complete.Followed by dropwise addition of 48percent by weight of 48percent fluoroboric acid at a temperature of -15 to -10 ° C (the mass percentage refers to the mass of fluoroboric acid as a percentage of the total mass of the fluoroboric acid reagent) Heated to 25 ° C crystallization 4h; filter, filter cake washed once, get wet goods 1337g.5-Amino-2-bromo-benzotrifluoride (48gm., 0.20 moles) was taken in autoclave reactor and reaction mass was cooled to - 10°C. The anhydrous hydrofluoric acid (104gm., 5.2moles) was added to the reaction mass and the temperature of the reaction mass was maintained at - 5°C. The sodium nitrite (15gm., 0.22moles) was added to the reaction mixture in small portions. After complete addition of sodium nitrite, the reaction mass was stirred at - 5°C to 0°C for 1.0 hour. The reaction mass was heated to 125°C and the temperature was maintained for 30 minutes. The reaction mixture is poured into cooled water and the title product was isolated. Yield (percent): 80percentIn a 2000ml three-necked flask, 400g of concentrated sulfuric acid, 400 g of m-fluorobenzotrifluoride, 2 g of lithium bromide, 20 g of ferric bromide, 20 g of tetrabutylammonium bromide, 234.1 g of bromine, Control temperature 20-25 , reaction 8h, sampling, GC detection of raw materials 0.72percent. Cooling to below 30 , Transferred to 5000ml separation funnel, stationary 1h, the acid was separated, the crude product was placed in 2000ml bottle, 1000g of water was added under stirring, and 10percent sodium hydroxide solution was added dropwise to adjust PH = 7 to obtain 551g of crude product which was still isolated, yield 92.9percent, 95.3percentThe product was distilled under reduced pressure 512.98g, distillation yield 93.09percent.In a 1000 mL three-necked flask, Under normal temperature and pressure conditions, 100 g of 100percent sulfuric acid, 200 g of m-fluorobenzotrifluoride, 4 g of ammonium bromide, 2 g of bromosuccinimide, 4 g of tetrabutylammonium bromide, Bromine was added dropwise 97.5g, After the addition, Control room temperature and pressure conditions, Continue to react 5-6h, sampling, GC detection of raw materials is less than 1percent.Stop the reaction, The catalyst is filtered off, Transferred to 1000mL separation funnel, Still 1h, Separate the acid, The crude product was placed in 1000mL bottle, 500g of water was added with stirring, Dropping 5percent sodium hydroxide solution to adjust PH = 7, After alkaline washing and desolventizing, Distillation collected 158-162 ° C / mmHg fractions, Get the final product 278g, Yield 92.3percentContent of 99percent.General procedure: (0262) With due modification of the starting compounds, the compound of formula V or Va can be prepared by procedures as given in below schemes. (0263) Step (A) (0264) A stirred solution of substituted trifluoromethyl benzene (1 eq.) in a solvent such as n-butanol, iso-butanol, n-propanol, iso-propanol (3 to 15 volume of formula II) was degassed at temperature range of 55C to 120C. To the stirred solution was added a base (0.8 to 5 equivalent of formula II), vinyl ether, metal (1 :0.001 to 1 :0.07 equivalent of formula II) and phosphine compound (0 to 0.25 equivalent of formula II). The reaction was again degassed and subsequently heated to 70C - 100C. The reaction mixture was stirred for 10-18 hours at 100C. After the completion of the reaction, the temperature of the reaction mixture was bought to 25C and the mixture was filtered through celite bed. The celite bed was washed with solvent such as n- butanol and filtrate was concentrated to obtain the desired coupled product.

Molecular Weight:243.00
XLogP3:3.6
Hydrogen Bond Acceptor Count:4
Exact Mass:241.93543
Monoisotopic Mass:241.93543
Heavy Atom Count:12
Complexity:156
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes