AKOS MSC-0782

White to off-white crystalline powder

The thermal characteristics of this reaction were studied using an HEL Simular reaction calorimeter. The calorimeter was equipped with a double-jacketed, 0.8-liter, glass reactor (6 bars). The inner jacket contained a heat-transfer fluid and the outer jacket was evacuated to insulate the system. A quantity of 26.5 g (0.139 moles, 1 equivalent) of 3-bromochlorobenzene (10), 200 ml of 2-methyltetrahydrofuran (Me-THF) and 15.0 g (0.158 moles, 1.1 equivalents) of anhydrous magnesium chloride was charged to this reactor. The slurry was then cooled to -78° C. A quantity of 91.2 ml (0.158 moles, 1.3 equivalents) of lithium diisopropylamide (LDA, 2M in heptane/THF) was charged into the batch, keeping the tempi). A 1.6 molar solution of butyllithium in hexanes (4.5 mL, 2.8 mmol) was placed in a three-neck flask equipped with a STIRRER, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0 °C. A solution of diisopropyl amine (1.13 mL, 8.1 mmol) in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0 °C for ten minutes, then cooled to-78 °C. Upon cooling, a solution of L-BROMO-3- chlorobenzene (1.4 g, 7.3 mmol) in anhydrous tetrahydrofuran was added dropwise. The reaction was allowed to stir at-78 °C for one hour. Anhydrous dimethylformamide (636 GEL) was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid (50 mL) and water (50 mL). The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 9: 1 hexanes: ethyl acetate to yield 2-chloro-6-bromobenzaldehyde as an off white solid (850 mg, 53 percent yield). NMR (300 MHz, CDC13): 10.4 (s, 1H), 7.6 (m, 1H), 7.45 (m, 1H), 7.3 ppm (m, 1H).Preparation of 2-bromo-6-chlorobenzaldehyde (i-5b). To a solution of l-bromo-3-chlorobenzene (i-5a) (5 g, 26. mmol) in THF (50 mL) was added LDA (1 M, 31.3 mL, 8.7 mmol) dropwise via an addition funnel at -70 °C. The mixture was stirred at -70 °C for 1 h. DMF (2.87 mL, 39.1 mmol, 227 mmol) in THF (20 mL) was added dropwise maintaining the internal temperature below -70 °C. The reaction was stirred vigorously at -70 °C for 1 h. Warmed to -30 °C, the reaction was poured into 1 M HCl (100 mL) partitioned between water (10 mL) and DCM (30 mL). The aqueous layer was extracted with DCM (20 mL x 3). The combined organic layers were dried over anhydrous Na

Molecular Weight:219.46
XLogP3:2.7
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:217.91341
Monoisotopic Mass:217.91341
Topological Polar Surface Area:17.1
Heavy Atom Count:10
Complexity:129
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes