Application of 1338226-21-3, New Advances in Chemical Research in 2021. Chemo-enzymatic cascade processes are invaluable due to their ability to rapidly construct high-value products from available feedstock chemicals in a one-pot relay manner. 1338226-21-3, name is 3-(Chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one, molecular formula is C4H6ClN3O, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, below Introduce a new synthetic route.
To a 75L flask was charged a 9.63wt% solution of 3-(chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one in NMP (11.6 kg,7.55 mol), 3 -chloro-5 -((2-oxo-4-(trifluoromethyl)- 1 ,2-dihydropyridin-3 -yl)oxy)benzonitrile (2.00 kg, 6.29 mol), NMP (3.8 L) and 2-methyl-2-butanol (6.0 L). To the resulting suspension was slowly added N,N-diisopropylethylamine (4.38 L, 25.2 mol) over 4h. The reaction was aged 18h at ambient temperature. The reaction is considered complete when HPLC indicated <1% 3 -chloro-5 -((2-oxo-4-(trifluoromethyl)- 1 ,2-dihydropyridin-3 -yl)oxy)benzonitrileremaining. The tan solution was quenched with acetic acid (1.26 L, 22.0 mol) and aged at ambient temperature overnight. The tan solution was warmed to 70 C. Water (2.52 L) was added and the batch was seeded with anhydrate Form 11(134 g)(procedures for making anhydrate Form II are described in W02014/052171). The thin suspension was aged lh at 70C. Additional water (14.3 L) was added evenly over 7 h. The slurry was aged 2h at 70 C andthen slowly cooled to 20 C over 5 h. The slurry was filtered and washed with 2 :1 NMP/water(6 L), followed by water washes (6 L x 2). The filter cake was dried under N2 to give 2.53 kg(85% yield) of a white solid that was confirmed to be crystalline Form II of the title compoundby X-ray powder defraction analysis.
The result showed that such a combination of chemo- and biocatalysis improved the catalytic yield more than two times compared with that of sole metal catalysis.I hope my blog about 3-(Chloromethyl)-4-methyl-1H-1,2,4-triazol-5(4H)-one is helpful to your research.
Reference:
Patent; MERCK SHARP & DOHME CORP.; CAO, Yang; GAUTHIER, Donald, R., Jr.; HUMPHREY, Guy, R.; ITOH, Tetsuji; JOURNET, Michel; QIAN, Gang; SHERRY, Benjamin, D.; TSCHAEN, David, M.; WO2015/84763; (2015); A2;,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics