Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 14804-31-0, name is 4-Bromo-1-methoxy-2-methylbenzene, A new synthetic method of this compound is introduced below., Application In Synthesis of 4-Bromo-1-methoxy-2-methylbenzene
Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10¡Á250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.
The synthetic route of 14804-31-0 has been constantly updated, and we look forward to future research findings.
Reference:
Article; Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W.; Bioorganic and Medicinal Chemistry Letters; vol. 25; 3; (2015); p. 690 – 694;,
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