Category: 38573-88-5

38573-88-5, These common heterocyclic compound, 38573-88-5, name is 1-Bromo-2,3-difluorobenzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

Under nitrogen atmosphere, diisopropylamine (25.2 g) was dissolved in THF (130 mL) and cooled to -70 ¡ã C. or lower. To the solution, a 1.6 M butyl lithium / hexane solution (130 mL) was added dropwise at a rate such that the internal temperature did not reach -65 ¡ã C., and then the mixture was stirred at -70 ¡ã C. or less for 30 minutes. Subsequently, a solution prepared by dissolving 2,3-difluorobromobenzene (40 g) in THF (150 mL) was added dropwise to the stirring reaction solution at a rate such that the internal temperature did not exceed -65 ¡ã C., For 1 hour. Subsequently, a solution of DMF (22.7 g) dissolved in THF (220 mL) was added dropwise at a rate such that the internal temperature did not become -65 ¡ã C. or higher, followed by stirring at -70 ¡ã C. or lower for 1 hour, then slowly And the mixture was heated to room temperature. 10percent hydrochloric acid and toluene were added to the reaction solution, the organic layer was separated, and the organic layer was washed with saturated brine. Sodium sulfate was added to the organic layer after washing and dried, and then the solvent was distilled off under reduced pressure to obtain a crude product (44.9 g) of 4-bromo-2,3-difluorobenzaldehyde.

Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 38573-88-5.

Reference:
Patent; DIC CORPORATION; TOJO, KENTA; KUSUMOTO, TETSUO; TAKATSU, HARUYOSHI; (13 pag.)JP6019595; (2016); B2;,
Bromide – Wikipedia,
bromide – Wiktionary

As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 38573-88-5 name is 1-Bromo-2,3-difluorobenzene, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below. 38573-88-5

(6S,9R)-6-(2,3-Difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one. See Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 1360-1370. In an oven-dried 1 L flask was Sodium tert-butoxide (13.19 g, 137 mmol), PALLADIUM(II) ACETATE (0.948 g, 4.22 mmol), and 2-(Dicyclohexylphosphino)-2′-methylbiphenyl (1.539 g, 4.22 mmol) weighed in a nitrogen bag. (R)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one (35.21 g, 106 mmol), Toluene (106 mL) (degassed in the original bottle by nitrogen gas), and 1-bromo-2,3-difluorobenzene (14.18 mL, 127 mmol) were added under nitrogen. The flask stirred at 80¡ã C. in a pre-heated oil bath for 20 h. Volatiles were stripped off and the residue was partitioned between EtOAc (400 ml) and water (400 ml). The layers were separated. The aqueous layer was extracted with EtOAc (50 ml). The combined organic layer was washed with brine, dried and concentrated to a dark oil. It was passed through a plug of silica gel (loaded with CH2Cl2 and eluted with EtOAc/hexane up to 30percent EtOAc). The crude product was obtained as a dark red oil (86percent mass recovery),. 1H NMR showed approximately 6/1 ratio of the desired trans isomer to the cis isomer. MS(ESI)[M+H+]=446.21.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 1-Bromo-2,3-difluorobenzene, and friends who are interested can also refer to it.

Reference:
Patent; Bristol-Myers Squibb Company; US2009/258866; (2009); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 38573-88-5, name is 1-Bromo-2,3-difluorobenzene, A new synthetic method of this compound is introduced below., 38573-88-5

4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole 3b (1.22 g, 5 mmol) was dissolved in 20 mL of tetrahydrofuran under stirring under an argon atmosphere, and 1-bromo-2,3-difluoro-benzene (0.97 g, 5 mmol), tetrakis (triphenylphosphine) palladium (0.17 g, 0.15 mmol) and 7 mL of sodium hydroxide solution (2M) were then added to the solution. Upon completion of the addition, the reaction system was stirred at 75¡ãC in an oil bath overnight. The reaction was completed until TLC showed the disappearance of starting materials. The reaction mixture was naturally cooled down to room temperature and extracted with ethyl acetate (20 mL*3). The combined organic extracts were washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The resulting solid was purified by silica gel column chromatography to give the title compound 4-(2,3-difluoro-phenyl)-1H-indole 3c (800 mg, yield 70percent) as a white solid. MS m/z (ESI): 228.4[M-1]

The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.

Reference:
Patent; Jiangsu Hengrui Medicine Co., Ltd.; Shanghai Hengrui Pharmaceutical Co. Ltd.; EP2179998; (2010); A1;,
Bromide – Wikipedia,
bromide – Wiktionary

Some common heterocyclic compound, 38573-88-5, name is 1-Bromo-2,3-difluorobenzene, molecular formula is C6H3BrF2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. 38573-88-5

EXAMPLE 200 Step-1: n-Butyl lithium (0.895 g, 0.0140 mol, 1.6 M in hexane) was added dropwise to a stirred solution of 2, 3-difluorobromobenzene (3.0 g, 0.0155 mol) in THF (40 ml) over a period of 20 min at -78 0C, and reaction was continued stirring for 2 h at the same temperature. Then, 4,6-dichloropyrimidine (2.316 g, 0.0155 mol) in THF (20 ml) was added drop wise to the generated 2,3-difluorophenyl lithium mixture over a period of 15 min at -78 ¡ãC, and reaction was continued stirring for 30 min. Then, the reaction mixture was slowly warmed to 0 ¡ãC and was quenched with water (30 ml), and then DDQ (3.53 g, 0.0155 mol) in THF (30 ml) was added portionwise with stirred for 10 min. The resultant reaction mixture was extracted with CH2Cl2 (3×50 ml), washed with brine (50 ml), dried (Na2SO4), and concentrated. The concentrated product was purified through silica column chromatography using pet. ether to afford step-1 product (1.1g, 27.1 percent) as an off white solid. Rf: 0.3 (100percent PE). 1H NMR (400 MHz, CD3OD): delta 8.82 (s, IH), 7.91-7.78 (m, IH), 7.48-7.45 (m, IH), 7.32-7.26 (m, IH). m/e (M+l): 260.8

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 38573-88-5, its application will become more common.

Reference:
Patent; MIIKANA THERAPEUTICS, INC.; WO2008/154026; (2008); A1;,
Bromide – Wikipedia,
bromide – Wiktionary