Reference of 36692-49-6, 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. 36692-49-6, name is Methyl 3,4-diaminobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.
A solution of methyl (4-fluorophenyl)(oxo)acetate (50.0 g, 275 mmol) and methyl 3,4- diaminobenzoate (46.9 g, 282 mmol) in ethanol (2.5 L) was heated to reflux for 2 d. The mixture was cooled to rt and most of the ethanol was removed in vacuo to form a thick paste. 0.5 L of THF was added to get a stirrable slurry and the slurry was stirred for 1 h, diluted further with 1 L of ether and solid was collected by filtration (50.0 g, 76.3%) as a mixture of regioisomers.To a solution of methyl 2-(4-fluorophenyl)-3-oxo-3,4-dihydroquinoxaline-6-carboxylate(50.0 g, 168 mmol) (mixture of regioisomers) in THF (0.9 L) and methanol (0.9 L) at rt was added 2.0 M of sodium hydroxide in water (300 mL). The reaction mixture was stirred at 70 C for 2 h. The mixture was allowed to cool slightly and some solids formed. The reaction mixture was filtered while warm to afford a clear orange solution. The filtrate was stirred with mechanic stirring. IN HC1 aqueous solution (~ 450 rtiL) was slowly added (over 15 min) to pH=8. The suspension was stirred for 5 min, filtered, washed with 100 mL of 1:1 MeOH:THF, dried to give a light yellow solid. [In some cases, there is still some undesired isomer present at this point. If so, the material was redissolved in methanol/THF mixture (14 mL per gram of each solvent) and 1 N NaOH (4.2 equivalents), and then reprecipitated to pH = 8 using 1 N HC1. This dissolution/reprecipitation procedure can be repeated until the pure desired regioisomer is obtained.] To the solid was added 300 mL of methanol, 300 mL of THF, and 250 mL of IN NaOH and the resulting solution was stirred by mechanical stirring until dissolved. The resulting solution was adjusted to pH=2.5 by adding IN HC1. The precipitate was collected by filtration, transferred to a round bottom flask using MeOH, evaporated in vacuo, and azeotroped with MeCN. The resulting solid was dried in vacuum pump to give a pure acid product (26.3 g, 55.2%) as a beige powder. LCMS (ESI+): m/z = 285.0 (M+H). H NMR (400 MHz, DMSO-6) delta 13.34 (s, 1H), 12.76 (s, 1H), 8.44 (dd, J= 9.1, 5.8 Hz, 2H), 7.96 – 7.89 (m, 2H), 7.83 (dd, J= 8.4, 1.8 Hz, 1H), 7.35 (t, J= 9.0 Hz, 2H).
The synthetic route of Methyl 3,4-diaminobenzoate has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MILLENNIUM PHARMACEUTICALS, INC.; GIGSTAD, Kenneth, M.; CARDIN, David, P.; HIRAYAMA, Takaharu; HIROSE, Masaaki; HU, Yongbo; KAKEI, Hiroyuki; LEE, Hong, Myung; MOTOYAJI, Takashi; NII, Noriyuki; SHI, Zhan; VYSKOCIL, Stepan; WATANABE, Hiroyuki; WO2015/161142; (2015); A1;,
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