Electric Literature of 589-10-6, These common heterocyclic compound, 589-10-6, name is (2-Bromoethoxy)benzene, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
EXAMPLE 2; PREPARATION OF 4-CHLORO-5-METHOXY-2-(2-PHENOXYETHYL)INDAN-l-ONE; 4-Chloro-5-methoxyindan-l-one (14.0 kg, 71.2 mol) (Example 1) was slurried in n- heptane (154 L). Glacial acetic acid (2.14 kg, 35.6 mol) was then added followed by 1,1- dimethylhydrazine (6.42 kg, 106.8 mol) such that the temperature remained <40C. The batch was then heated to 900C for 3 h. The batch was cooled to 600C, treated with THF (28 L) then concentrated to 40 L by distillation under atmospheric pressure. The resulting concentrate was cooled to 500C and diluted with THF (182 L). The THF solution was held overnight at <15C. The batch was cooled to -500C by direct injection of liquid N2, then n-hexyllithium (2.39 M in hexane, 21.2 kg, 71.2 mol) was added over 1.5 h, maintaining the internal temperature <-25C. The resulting slurry was aged between -30 and -200C for 30 min then a solution of beta-bromophenetole (14.4 kg) in THF (14 L) was added over 5 min, maintaining the internal temperature <-25C. The batch was then aged at -50C for 30 min. 6 N HCl (30 kg 37% HCl + 30 kg H2O) was charged to the mixture which was then aged at 500C until complete hydrolysis of the intermediate hydrazone was confirmed by HPLC (1.5 h). After cooling the batch to 200C, isopropyl acetate (56 L) was added and the aqueous layer was discarded. The organic phase was washed with water (75 L) then concentrated to 40 L using vacuum distillation at 4O0C. n-Heptane (40 L) was added and after aging for 30 min at 400C, 0.2% seed of the product ketone was added. The mixture was stirred for 1 h to allow a seed bed to develop, then a further 80 L of n-heptane was charged over 1 h at 400C. The resulting slurry was allowed to cool to 200C overnight then cooled to 5C over 1 h before filtering. The filter cake was washed with 4:1 heptanerisopropyl acetate (25 L), then sucked dry under a stream OfN2 for 3 h. The solid was dried in a vacuum oven at 45C for 48 h affording 20.2 kg of product as an off white solid in 88% yield. 1H NMR (400 MHz, CDCl3) delta 7.70 (IH, d, J = 8.4 Hz), 7.35-7.25 (2H, m), 7.04-6.88 (4H, m), 4.25-4.15 (2H, m), 4.00 (3H, s), 3.46-3.35 (IH, m)> 2.98-2.87 (2H, m), 2.54-
The synthetic route of 589-10-6 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MERCK & CO., INC.; MERCK SHARP & DOHME LIMITED; WO2007/81895; (2007); A2;,
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