3-BROMO-5-FLUOROBENZALDEHYDE

Ice bath, the 2M Isopropylmagnesium chloride (10 mL, 20 mmol) was dissolved in 5 mL of tetrahydrofuran, A solution of 1, 3-dibromo-5-fluorobenzene 40a (4.0 g, 15.70 mmol) In tetrahydrofuran, Stirred for 2 hours, and then heated to 20 ° C reaction for 30 minutes. Cool down to 0 ° C, N, N-Dimethylformamide (2.5 mL, 31.50 mmol) was added dropwise, The reaction was stirred for 1.5 hours, The reaction was stirred at room temperature for 12 hours.The reaction was quenched by the addition of 20 mL of saturated ammonium chloride solution, extracted with ethyl acetate (50 mL of X3) and the organic phases were combined, dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure and eluted with silica gel column chromatography eluent system B The resulting residue was purified to give the title product 3-bromo-5-fluorobenzaldehyde 40b (2.57 g, yellow liquid), yield: 81.0percent.3-Bromo-5-fluorobenzaldehyde. To a solution of (3-bromo-5-fluorophenyl)methanol (2 g, 9.75 mmol) and triethylamine (2.72 mL, 19.5 mmol) in dimethylsulfoxide (25 mL) at 10° C. was added sulfur trioxide-pyridine (3.11 g, 19.5 mmol) in several portions. The mixture was stirred at room temperature for 30 min. The reaction was poured into ice water/pentane and the layers separated. The organics were washed with 1 M potassium bisulfate, then water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (3percent ethyl acetate/hexanes) gave 1.45 g (73percent) as a white solid. 3-bromo-5-fluorobenzaldehyde (A) To a solution of 3-bromo-5-fluorobenzaldehyde (15 g, 73.89 mmol, 1 eq) in DCM (150 ml) was addedDAST (39 ml, 295.5 mmol 4 eq) dropwise at -78°C and the mixture was stirred at RT for 16 h. Aftercompletion of the reaction, the mixture was poured into ice-cold water and basified with sat. NaHCO3solution. The mixture was then extracted with DCM (3 x 200 ml), washed with water (200 ml) and brine (200 ml), dried (Na2SQ4), and concentrated in vacuum to give the crude product, which was purified by flash chromatography to afford 1 -bromo-3-(difluoromethyl)-5-fluorobenzene (10 g, 60percent).Example 13-Difluoromethyl-5-(2, 3-difluoro-6-nitrophenoxy)benzonitrile (FIGURE 2;ROUTE A).; step 1 - To a solution of o-propylmagnesium chloride in THF (500 mL of a 2M solution in THF, 1.0 mol) and THF (200 mL) was added a solution of 3, 5- dibromofluorobenzene (25; 200 g, 0.79 mol) in THF (100 mL) while maintaining the temperature at ca. 0 C. After rinsing with THF (3 x 20 mL) the mixture was aged for 2 h at ca. 0 Synthesis of ethyl-2-(3-bromo-5-fluorobenzylidene)-3-oxobutanoate (Mix of E and Z) To a solution of

Molecular Weight:203.01
XLogP3:2.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:201.94296
Monoisotopic Mass:201.94296
Topological Polar Surface Area:17.1
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes