Electric Literature of 883499-24-9, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 883499-24-9, name is 1-Bromo-2-chloro-3-fluorobenzene belongs to chlorides-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.
To a mechanical-stirred solution of diisopropylamine (5.02 g, 7.08 ml, 49.7 mmol, Eq:1.04) in THF (35 ml) was added dropwise (5 mm) at -20C n-butyllithium, 1.6 M in hexane (31ml, 49.7 mmol, Eq: 1.04) and stirred at 0 C for 20 minutes. The mixture was cooled to -78 Cfollowed by dropwise addition (20 minutes) of a solution of 1-bromo-2-chloro-3-fluorobenzene(10 g, 47.7 mmol, Eq: 1) in THF (10 ml) and the thick yellow suspension was stirred at -78 Cfor 60 mm. Then was added dropwise (5 minutes – exotherm) N,N-dimethylformamide (5.23 g,5.55 ml, 71.6 mmol, Eq: 1.5), the cooling bath was removed and the mixture was allowed to warm to -20 C to give complete conversion. At -20 C the clear yellow solution was quenched with sat NH4C1 (100 ml) and extracted with TBME (100 ml). The aqueous layer was extracted again with TBME (50 ml). The organic layers were dried and evaporated at only 50 mbar forshort time. The yellow residue was dissolved in heptane/ethyl acetate 10:1 (ca. 30 ml) at 55 C,concentrated to 1/3 and stirred to 22 C while crystallisation started. After 30 minutes thesuspension was cooled to 0 C for 30 minutes, the solid was filtered off, washed with heptane (2x 15 ml) and dried (only short time) to give 4-bromo-3-chloro-2-fluorobenzaldehyde (5.27 g,47%) as light yellow solid. The filtrate was evaporated and purified by flash chromatography (silica gel, 70 g, adsorbed on isolute sorbent HM-N, EtOAc in heptane, 0% to 5% ) to give additional compound (4.073 g, 36%) as off-white solid.GC-MS: mlz = 235.9 M.+ (monoisotopic mass 235.90)
The synthetic route of 1-Bromo-2-chloro-3-fluorobenzene has been constantly updated, and we look forward to future research findings.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; HOFFMANN-LA ROCHE INC.; ALANINE, Alexander; BEIGNET, Julien; BLEICHER, Konrad; FASCHING, Bernhard; HILPERT, Hans; HU, Taishan; MACDONALD, Dwight; JACKSON, Stephen; KOLCZEWSKI, Sabine; KROLL, Carsten; SCHAEUBLIN, Adrian; SHEN, Hong; STOLL, Theodor; THOMAS, Helmut; WAHHAB, Amal; ZAMPALONI, Claudia; (623 pag.)WO2017/72062; (2017); A1;,
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