A common heterocyclic compound, 3543-73-5, name is Ethyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate, molecular formula is C14H19N3O2, 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. 3543-73-5.
To a solution of 81.3 g (650.6 mmol) 2-bromoethanol, 1 g potassium iodide and 100 g water was added 17.0 g (65 mmol) compound (6). The reaction mixture was heated to 65-70 C. and held at this temperature for 8 h to 12 h. The pH value of the solution was held between 4.2-5.5 during this period by dropwise addition of a solution of 20.0 g (151.4 mmol) diammonium hydrogen phosphate in 35 g water. The control of pH over the duration of the reaction was effected through use of a pH electrode. The conversion was followed by HPLC. The reaction was continued until the fraction of compound (7A) was ?1.5%. Thereby ca. 8% of compound (7B) had formed and the proportion of compound (7) was ca. 87%. The reaction mixture was subsequently concentrated to dryness at ca. 55-60 C. under vacuum. To the residue was added 150 g water and, preferably with an alkali metal carbonate, the pH value adjusted to ca. 8.5. The desired product (7) was extracted with 200 g methylene chloride or 225 g chloroform, and the organic phase subsequently washed with 60-80 g water. The organic phase was then concentrated to dryness and the remaining oil or already crystalline residue dissolved in 200 g ethyl acetate or alternatively in 60 g acetonitrile. Compound (7) crystallised at ca. 5 C. and was filtered under suction, washed with 20 g cold ethyl acetate or alternatively with 15 g cold acetonitrile and dried at 60-70 C. The yield of compound (7) was 18.3 g (52.4 mmol) with a content of ?98.2% (80.5% of theory). The crude contained ?0.6% compound ( 7A) and compound (7B) respectively as well as <0.15% of compound (7C). The crude product obtained was recrystallized from ethyl acetate, or alternatively from acetonitrile, toluene, propan-2-ol, tetrahydrofuran, acetone, isopopyl acetate or water, prior to further conversion to compound ( 8). Thereby the yield of compound (7) was 17.2 g (94.0% recrystallization yield) with a content of >99.2%, wherein compound (7A) was removed below a content of 0.2% and compound (7B) below 0.3%. Through the course of the reaction, the content of compound (7C) was kept below 0.15%, as this compound can only poorly be removed by recrystallization from the above described solvents. The overall yield of this step was 76.5% of theory and was thus ca. 12.5% higher than that described in the procedure using ethylene oxide as according to DD34727 and ca. 31% higher in comparison to the favoured procedure of WO2011079193 involving addition of Huenig’s base.
The synthetic route of Ethyl 4-(5-amino-1-methyl-1H-benzo[d]imidazol-2-yl)butanoate has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Heyl Chemisch-pharmazeutische Fabrik GmbH & Co. KG; Frey, Michael; Walther, Dirk-Detlef; US2014/31560; (2014); A1;,
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