4-Bromo-2,6-difluorobenzaldehyde

H-BuLi (2.7M solution in heptane, 134 mL, 0.36 mol) was added drop wise at -75 Step: 1 4-bromo-2, 6-difluorobenzaldehyde To a solution of l-bromo-3, 5-difluorobenzene (Cas No. 461-96-1, 210 g, 1.09 mol, 1.0 eq) in anhydrous THF (1000 mL), LDA/THF (545 mL, 1.09 mol, 1.0 eq, 2 M) was added slowly under nitrogen atmosphere at -78 °C. The reaction solution was stirred for 2 h at -78 °C, and then anhydrous DMF (79.6 g, 1.09 mol, 1.0 eq) was added dropwise. The reaction was stirred for 15 min at -78 °C and then a solution of AcOH in ethyl acetate (1/1, 300 mL) was added to adjusted pH = 4-5 at -78 °C. The reaction mixture was stirred at rt for 15 min, concentrated under reduced pressure, diluted with ethyl acetate (1000 mL) and washed with brine (600 mL x 2). The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure and recrystallized from w-hexane to give the title compound (106 g, yield: 44percent) as a light yellow solid. 1H NMR (400 MHz, CDC1Under a nitrogen atmosphere, 2, 2, 6, 6-tetramethylpiperidine (29.3 g) was dissolved in THF (130 mL)It was cooled below -70 ° C. To the solution, a 1.6 M butyllithium / hexane solution (130 mL) was added dropwise at such a rate that the inner temperature did not reach -65 ° C., and then the mixture was stirred at -70 ° C. or lower for 30 minutes. Subsequently, a solution prepared by dissolving 3, 5-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 ° C., For 1 hour. Subsequently, a solution of DMF (22.7 g) dissolved in THF (220 mL) was added dropwise at such a rate that the internal temperature did not become -65 ° C. or higher, followed by stirring at -70 ° 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 to separate the organic layer, 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 of 4-bromo-2, 6-difluorobenzaldehyde (29.7 g).Google Translate for Business:Translator ToolkitWebsite TranslatorGlobal Market FinExample A-14; 2-(4-bromo-2, 6-difluorophenyl)-4-(4-methoxyphenyl)-1H-imidazole-5-carboxamide; Step a - 4-bromo-2, 6-difluorobenzaldehyde; 0.7 g (7.7 mmol 10 eq) of manganese dioxide is added to a solution of 1.0 g (0.77 mmol, 1 eq) of 2, 6-difluoro-4-bromobenzylalcool in 15 mL of dichloromethane. The reaction medium is stirred at room temperature for 48 hours.The solid is filtered off and the solvent is evaporated off. The residual oil is chromatographed on silica gel (8/2 heptane/ethyl acetate) and 760 mg of 4-bromo-2, 6-difluorobenzaldehyde are obtained. Yield = 76percent55 ml (0.11 mmol) of 2 M lithium diisopropylamide are added with stirring at -70° C. to a solution of 19.3 g (0.1 mmol) of 1-bromo-3, 5-difluorobenzene in 120 ml of dried tetrahydrofuran.After 30 minutes, N-formylpiperidine is added dropwise at this temperature.The mixture is allowed to warm to 0° C. To a solution of 1-bromo-3, 5-difluorobenzene (Cas No. 461-96-1, 210 g, 1.09 mol, 1.0eq) in anhydrous THF (1000 mL), LDA/THF (545 mL, 1.09 mol, 1.0 eq, 2 M) was added slowly under nitrogen atmosphere at -78 °C. The reaction solution was stirred for 2 h at -78 °C, and then anhydrous DMF (79.6 g, 1.09 mol, 1.0 eq) was added dropwise. The reaction was stirred for 15mm at -78 °C and then a solution of AcOH in ethyl acetate (1/1, 300 mL) was added to adjusted pH = 4-5 at -78 °C. The reaction mixture was stirred at ft for 15 mm, concentrated under reduced pressure, diluted with ethyl acetate (1000 mL) and washed with brine (600 mL x 2). The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure andrecrystallized from n-hexane to give the title compound (106 g, yield: 44percent) as a light yellowsolid. ‘H NMR (400 MHz, CDC13) (5: 10.29 (s, 1H), 7.23 (s, 1H), 7.21 (s, 1H); ESI-MS (M+H):220.9, 222.9.

Molecular Weight:221.00
XLogP3:2.3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:219.93353
Monoisotopic Mass:219.93353
Topological Polar Surface Area:17.1
Heavy Atom Count:11
Complexity:141
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes