5-BROMO-2,3-DIFLUORO-BENZALDEHYDE

To a stirred solution of 2, 3-difluorobenzaldehyde (XVIII) (75.0 g, 528 mmol, 1.0 eq) in H2S04 (565 mL) was added NBS (113 g, 633 mmol, 1.2 eq) in portions at 60 °C. The resulting mixture was stirred at 60 °C for 12 hr. LC/MS showed the reaction was completed. The reaction mixture was poured into ice water and petroleum ether (500 mL) and stirred for 10 mm, the organic layer was separated and concentrated under vacuum to give cmde product. The residue was purified column chromatography silica gel (100percent petroleum ether) to give 5-bromo-2, 3- difluorobenzaldehyde (XIX) (120 g, 543.0 mmol, quantitative yield). ESIMS found C7H3BrF2O mlz 221.1 (M+1).[0617] To a stirred solution of 2, 3-difluorobenzaldehyde (XVIII) (75.0 g, 528 mmol, 1.0 eq) in HTo a stirred solution of 2, 3-difluorobenzaldehyde (XVIII) (75.0 g, 528 mmol, 1.0 eq) in H2SO4 (565 mL) was added NBS (113 g, 633 mmol, 1.2 eq) in portions at 60 °C. The resulting mixture was stirred at 60 °C for 12 hr. LC/MS showed the reaction was completed. The reaction mixture was poured into ice water and petroleum ether (500 mL) and stirred for 10 min, the organic layer was separated and concentrated under vacuum to give crude product. The residue was purified column chromatography silica gel (100percent petroleum ether) to give 5-bromo-2, 3- difluorobenzaldehyde (XIX) (120 g, 543.0 mmol, quantitative yield). ESIMS found CTo a stirred solution of 2, 3-difluorobenzaldehyde (XVIII) (75.0 g, 528 mmol, 1.0 eq) in HTo a stirred solution of 2, 3-difluorobenzaldehyde (XXIII) (75.0 g, 528 mmol, 1.0 eq) in HStep 1 (0813) To a stirred solution of 2, 3-difluorobenzaldehyde (XXIII) (75.0 g, 528 mmol, 1.0 eq) in HStep 1 followed the general procedure from Example 3 step 1. 2, 3-difluorobenzaldehyde (200 mg, 1.408 mmol) was dissolved in concentrated H2S04 (0.64 mL) and heated to 60 00. To this was added N-bromosuccinimide (301 mg, 1.690 mmol) in three portions over a period of 20 mm. After being heated for 3 h under argon, the reaction mixture was poured into ice water. The product was extracted with hexanes, washed with water and brine, and then dried over anhydrous Na2SO4. Purification by flash chromatography yielded an orange liquid as 2, 3- difluoro-5-bromobenzaldehyde (155 mg, 50percent yield), which was dissolved in 6 mL of methanol. To this stirring solution was added NaBH4 (32 mg, 0.84 mmol). The reaction was stirred for I h at room temperature. Then the reaction was diluted with ethyl acetate, washed with saturated aqueous NH4CI, followed by brine. The organic layer was dried over anhydrous Na2SO4, and evaporated under reduced pressure yielded 2, 3-difluoro-5-bromobenzyl alcohol as a white solid (163 mg, 87percent yield). The boronate product was then obtained from 2, 3-difluoro-5-bromobenzyl alcohol according to the general procedure of Example 1. The crude material was used for Suzuki coupling reaction without purification.Compound 1 (5.0 g, 3.5 mmol) was dissolved in concentrated H2SO4 (16 mL) and heated to 60 °C. N-bromosuccinimide (7.5, 4.2 mmol) was added in three portions over a period of 30 min. After being heated for 3 h under NStep I To a stirred solution of 2, 3-difluorobenzaldehyde (30 g, 211 mmol) in HAdd in 100mL three-necked bottles2, 3-difluorobenzaldehyde (1 g, 7.04 mmol) and concentrated sulfuric acid (50 mL), Stir at room temperature to obtain a brownish yellow reaction solution.Slowly add NBS (1.05g, 5.90mmol) in batches, add, The temperature was raised to 45-50 ° C for 2-3 h.The reaction solution was slowly added dropwise to 200 mL of ice water, and extracted twice with ethyl acetate (50 mL×2).The organic phases were combined and washed twice with saturated brine.Dry over anhydrous sodium sulfate for 30 min, filter, and concentrate the filtrate under reduced pressure.Got 280mg. Raw material recovery.

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:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes