2,3-DIFLUORO-4-BROMOBENZALDEHYDE

Preparation of iso-PrMgCl-LiCl-A sample of LiCl (4.56 g, 107.6 mmol) was dried under high vacuum with a heat gun for 10 min. To the dry solid under a NTo a solution of R-43c (1.29 mL, 10 mmol) in THF (5 mL) at -40° C. was added the iso-PrMgCl.LiCl solution (5.5 mL, 11 mmol, 2.0M in THF) at a rate that maintained the reaction temperature below -30° C. Stirring was continued at -35 to -30° C. for 1 h then warmed to -7° C. for an additional 1 h. The reaction mixture was cooled to -30° C. and DMF (1.00 mL, 13 mmol) was added in one portion (temperature rose to -23° C.) and stirring continued for 3.5 h at -25 to +15° C. The reaction mixture was poured into 1M HTo a solution of 23c (1.29 mL, 10 mmol) in THF (5 mL) at -40° C. was added the iso-PrMgCl.LiCl solution (5.5 mL, 11 mmol, 2.0M in THF) at a rate that maintained the reaction temperature below -30° C. Stirring was continued at -35 to -30° C. for 1 h then warmed to -7° C. for an additional 1 h. The reaction mixture was cooled to -30° C. and DMF (1.00 mL, 13 mmol) was added in one portion (temperature rose to -23° C.) and stirring continued for 3.5 h at -25 to +15° C. The reaction mixture was poured into 1M Hstep 3-Preparation of iso-PrMgClLiCl-; A sample of LiCl (4.56 g, 107.6 mmol) was dried under high vacuum with a heat gun for 10 min. To the dry solid under a NPreparation of iso-PrMgCl.LiCl-A sample of LiCl (4.56 g, 107.6 mmol) was dried under high vacuum with a heat gun for 10 min. To the dry solid under a NTo a solution of R-43c (1.29 mL, 10 mmol) in THF (5 mL) at -40° C. was added the iso-PrMgCl.LiCl solution (5.5 mL, 11 mmol, 2.0M in THF) at a rate that maintained the reaction temperature below -30° C. Stirring was continued at -35 to -30° C. for 1 h then warmed to -7° C. for an additional 1 h. The reaction mixture was cooled to -30° C. and DMF (1.00 mL, 13 mmol) was added in one portion (temperature rose to -23° C.) and stirring continued for 3.5 h at -25 to +15° C. The reaction mixture was poured into 1M HUnder a nitrogen atmosphere, 2, 2, 6, 6-tetramethylpiperidine (48.5 mL) and THF (250 mL) were put in a reaction vessel, and the resulting mixture was cooled to 0°C. Then, n-butyllithium (1.60 M; n-hexane solution; 178 mL) was slowly added thereto, and the resulting mixture was stirred for 1 hour. Next, the resulting mixture was cooled to -70°C, and then a THF (500 mL) solution of compound (T-1) (50.0 g) was slowly added thereto, and stirred for 1 hour, and then N, N-dimethylformamide (DMF) (40.1 mL) was slowly added thereto, and stirred for 12 hours while the mixture was returned to room temperature. The resulting reaction mixture was poured into a saturated aqueous solution of ammonium chloride, and the resulting aqueous layer was subjected to extraction with ethyl acetate. Then, organic layers combined were washed with brine, and dried over anhydrous magnesium sulfate. The resulting solution was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (hexane : ethyl acetate = 5 : 1 in a volume ratio). Then, the resulting product was further purified by recrystallization from a mixed solvent of hexane and ethyl acetate (1 : 1 in a volume ratio) to give compound (T-2) (46.9 g; 82percent).A crude product of NaBH4 (256.49 mg, 6.78 mmol) was added to a solution of Compound BD4-4 (500.00 mg, 2.26 mmol) in MeOH (4.00 mL). The mixture was stirred at 15C for 1 hour. TLC showed the reaction had completed. The mixture was concentrated to get crude residue and diluted with NaHCC 5 mL and extracted with EtOAc (5 mL * 3). The combined organic layers were washed with brine (5 mL * 3), dried over Na2SC>4, filtered and concentrated under reduced pressure to yield a residue. The residue was purified by prep-TLC (S1O2, petroleum etherethyl acetate mixture with a ratio of 5: 1) to afford Compound BD4-5 (300.00 mg, crude) as a yellow oil.

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