Background and overview[1]
Diethyl cyanomethyl phosphate, alias: diethyl cyanomethyl phosphate, diethyl cyanomethyl phosphate, colorless transparent liquid, density 1.095, boiling point 101-102°C, refractive index 1.4312-1.4332 , used to prepare 2-aminoquinoline. 2-Aminoquinoline can be used to prevent and/or treat depression, anxiety disorders, schizophrenia, panic disorder, agoraphobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, pain, memory impairment, dementia, and eating behavior disorders, sexual dysfunction, sleep disorders, substance abuse, movement disorders such as Parkinson’s disease, psychiatric disorders or gastrointestinal disorders.
Preparation[1]
Step 1,
Add chloroacetic acid to ethanol, add concentrated sulfuric acid under stirring, stop stirring after heating to reflux, react for 8 hours, filter and wash with water, separate the water layer, and obtain ethyl chloroacetate; add ethyl chloroacetate to ammonia water at 0°C After adding, stir for 15 minutes, cool, let stand, filter through Formosa Plastics Group, and dry to obtain chloroacetamide; then, add phosphorus pentoxide to chloroacetamide, heat and dehydrate, and steam out chloroacetonitrile while heating. Distill under reduced pressure to evaporate all the chloroacetonitrile; dry the obtained crude product with phosphorus pentoxide and magnesium oxide, and fractionate under reduced pressure to obtain the finished product of chloroacetonitrile.
Step 2,
Transfer the product chloroacetonitrile in step 1 to the synthesis reaction kettle, add the catalyst tetrabutylammonium iodide, heat to 80°C, and then drip in triethyl phosphite, and control the dripping speed according to the reflux size of the reaction. The internal temperature is controlled at 80°C, the dripping time is controlled to be completed in 8 hours, and the internal temperature is controlled at 110°C and the reaction is maintained for 8 hours. The reaction by-product, ethyl chloride, is recovered using cryogenic compression technology to obtain a crude product.
Step 3,
Transfer the crude product to a high-purity distillation tower for purification. According to the different boiling points of the materials, triethyl phosphite (applied) and diethyl cyanomethyl phosphate are distilled respectively. The residue from the distillation kettle is transferred to a special reaction kettle and treated with alkali before being sold as phosphorus and potassium fertilizer.
Apply[2-3]
Application 1,
CN201610910631.6 discloses a preparation process of (1R,2S)-1-cyano-2-(3,4-difluorophenyl)cyclopropane, wherein the preparation process includes the following steps: Step 1 ) In the presence of (S)-binaphthol phosphate, contact reaction between 3,4-difluorostyrene and hydrogen peroxide to obtain (2S)-2-(3,4-difluorophenyl)oxirane; step 2) In the presence of a base, react (2S)-2-(3,4-difluorophenyl)oxirane in 1,4-dioxane with diethyl cyanomethylphosphate to obtain the target product. This preparation process avoids the use of chiral starting materials, reduces reaction costs, and conveniently synthesizes (1R,2S)-1-cyano-2-(3,4- Difluorophenyl)cyclopropane has high overall yield and stereoselectivity, and the method is easy to operate and is suitable for industrial expansion of production.
Application 2,
CN201210417980.6 discloses a preparation method of 2-(imidazo[1,2-a]pyridin-3-yl)acetonitrile. The method includes the following steps: (1) 2,2-dimethoxy 4,4-dimethoxy-2-butenenitrile is prepared by the condensation reaction of acetaldehyde and cyanomethylphosphate diester; wherein, the reaction solvent is cyclohexane; the catalyst is sodium methoxide methanol solution; the reaction temperature is 0- 25°C, reaction time is 2-4 hours; (2) 4,4-dimethoxy-2-butenenitrile and 2-aminopyridine or its hydrochloride ring-closing reaction bactericidal preservative to prepare 2-(imidazo) [1,2-a]pyridin-3-yl)acetonitrile; wherein, in step “(1)”, the cyanomethyl phosphate diester is cyanomethyl phosphate dimethyl ester or cyanomethyl phosphate diethyl ester. The raw materials of the invention are easy to obtain, safe to use, have mild reaction conditions, strong controllability, low cost, good product quality and high yield, and are suitable for large-scale production.
