The important role of

Reference of 6136-93-2, These common heterocyclic compound, 6136-93-2, name is 2,2-Diethoxyacetonitrile, 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.

Sodium methylate (54 g, 1 mol) was added to a solution of diethoxyacetonitrile (139 ml_, 1 mol) in methanol (500 ml_). The reaction mixture was kept at room temperature for 24 g, then the reaction mixture was evaporated, treated with water (500 mL), and the product was extracted with ether (2×300 mL). The combined organic extracts were dried over anhydrous K2CO3 and evaporated to give 114.62 g (60% purity) of methyl 2,2- diethoxyethanimidoate. The obtained crude product was used for the next stage without additional purification.10% Pd/C (2 g) was added to a solution of 4,5-difluoro-2-nitroaniline (40 g, 0.229 mol) in methanol (500 mL). The reaction mixture was hydrogenated at room temperature for 3 h and treated with the mixture of compound methyl 2,2-diethoxyethanimidoate (71 g, 0.23 mol) with acetic acid (60 g). After 16 h at room temperature, the reaction mixture was evaporated, washed with the 10% K2CO3 solution (1 L), and the product was extracted with ether (300 mL). The organic extract was evaporated, and the residue was purified on silica gel (ethyl acetate/hexane 1 :5) to give 48 g of 2-(diethoxymethyl)-5,6-difluoro-1H-benzimidazole. Cs2CO3 (67.21 g, 0.206 mol) and methyl iodide (27 g, 0.19 mol) were added to a solution of 2-(DiethoxymethyI)-5,6-difluoro-1H-benzimidazoIe (48 g, 0.1875 mol) in DMF (250 mL). The reaction mixture was stirred at room temperature for 16 h and evaporated. Ethyl acetate (300 mL) was added to the residue, and the reaction mixture was washed with water (1 L). The organic layer was separated, dried, and evaporated. The residue was purified on silica gel (ethyl acetate/hexane 1 :5) to give 40.8 g of 2-(diethoxymethyl)-5,6-difluoro-1-methyl- 1 /-/-benzimidazole. 2-(Diethoxymethyl)-5,6-difluoro-1-methyl-1W-benzimidazole was treated with 5 M HCI (300 ml_), and the reaction mixture was kept at 60 0C for 6 h. Then the reaction mixture was evaporated to a volume of 100 ml_ and treated with acetone (200 mL). Then the mixture was kept in a refrigerator, and white crystals precipitated. The crystals were separated by filtration and dried under a reduced pressure to give 5,6-Difluoro-1-methyl-1H-benzimidazole-2- carbaldehyde Hydrochloride Hydrate in 72% (26.77 g, 21.4 g of free base) yield. Satisfactory C, H, lambda/-analysis was obtained.

The synthetic route of 6136-93-2 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; PFIZER PRODUCTS INC.; WO2007/135527; (2007); A2;,
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts