Electric Literature of 4457-67-4, A common heterocyclic compound, 4457-67-4, name is 1-Bromo-4-methoxybutane, molecular formula is C5H11BrO, 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.
(4-Methoxybutyl)(4-trifluoromethylphenyl)methanone (II) A dry three neck glass assembly, under dry nitrogen atmosphere, is charged with 150 g (6.17 moles) of magnesium and 2 L of anhydrous tetrahydrofuiran (THF). A small amount of iodine crystals or 1,2-dibromoethane is added to facilitate the initiation of Grignard reaction. The contents of the flask are heated to 75° C. and 975 g (5.84 moles) of 1-bromo-4-methoxybutane is added slowly at such a rate that the reaction maintains a spontaneous gentle reflux until the end of its addition. The Grignard reagent thus formed is cooled to 10 to 20° C. and a solution of 500 g (2.92 moles) of 4-trifluoromethylbenzonitrile in 2 L of tetrahydrofuran is introduced during a period of 1 hour to 2 hours while maintaining the reaction temperature at 16+-2° C. by external cooling, if necessary. Thereafter the temperature is raised gradually to 60 to 70° C. over a period of 1 hour and further continued at that temperature until the reaction has gone to completion. The reaction mass is cooled, then quenched into ice cold hydrochloric acid and the THF layer is separated and concentrated. The aqueous layer is further extracted with dichloromethane which is added to the concentrate of the THF layer. The resulting dichloromethane solution washed with brine, dried over anhydrous sodium sulfate, and the solvent evaporated under reduced pressure to obtain a crude product, which is further purified by high vacuum distillation. The compound (4-methoxybutyl)(4-trifluoromethylphenyl)methanone (II) is obtained in 71.84percent yield (546 g). Analytical data: m.p 40-42° C.(purified by distillation). 1H NMR: (CDCl3, 200 MHz); (delta) 1.66-1.87 (m, -(CH2)2-,4H); 3.04 (t, J=7.26 Hz, -(CH2)-, 2H); 3.33 (s, -OCH3, 3H); 3.43 (t, J=7.26 Hz, -(CH2)-, 2H); 7.72 (d, J=8.30 Hz, 2H); 8.06 (d, J=8.30 Hz, 2H).
The synthetic route of 4457-67-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Sun Pharmaceutical Industries Ltd.; US6380436; (2002); B1;,
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem