A catalytic protocol for the enantio- and diastereoselective reduction of α-substituted-β-keto carbonitriles is described The reaction involves a DKR-ATH process with the simultaneous construction of β-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers A wide range of α-substituted-β-keto carbonitriles were obtained in high yields (94%-98%) and excellent enantio- and diastereoselectivities (up to >99% ee, up to >99:1 dr) The origin of the diastereoselectivity was also rationalized by DFT calculations Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution.

Disclosed in the present invention are a method and an apparatus for continuous synthesis of cyclopropane compounds. The method comprises the following steps: the synthesis reaction of a diazomethane precursor is carried out continuously in a first reactor; the reaction product in the first reactor flows into a separator to perform stratification; the organic phase obtained by stratification overflows into a second reactor; in the second reactor, the diazomethane precursor is continuously consumed to prepare diazomethane, and an electron-rich monoolefin cyclopropanation reaction is performed in situ to obtain cyclopropane compounds. By applying the technical solution of the present invention, automatic control can be achieved, the transfer of high-risk materials can be reduced, and the risk of pipeline transfer of diazomethane solution can be prevented, so that production safety is effectively improved. Moreover, the apparatus is simple, so that the investment in the apparatus is reduced. The production of diazomethane and the cyclopropanation of olefins can be safely and quantitatively implemented simultaneously.

Method and apparatus for continuous synthesis of cyclopropane compounds

The present invention provides a process of preparing diazomethane. The process comprises: step S1, using N-methylurea as a raw material to continuously prepare a first product system containing N-methyl-N-nitrosourea in a continuous reactor; step S2, extracting and back-extracting the first product system continuously to obtain a N-methyl-N-nitrosourea solution; step S3, continuously reacting the N-methyl-N-nitrosourea solution with an alkali solution in a continuous reactor to obtain a second product system containing diazomethane; and step S4, continuously performing liquid separation and water removal by freezing on the second product system to obtain the diazomethane. A 2-methyltetrahydrofuran solution of MNU is obtained through a completely continuous reaction and posttreatment by using N-methylurea as a raw material, and then an anhydrous diazomethane solution is directly obtained through a completely continuous reaction and posttreatment. Water is removed by a freezing technology, and use of an expensive semipermeable membrane or liquid-liquid separator is avoided, so that the cost is lower.

Process of preparing diazomethane

The invention relates to a method and equipment for preparing diazomethane, and belongs to the field of organic synthesis. The method and the equipment have the advantages that the method and the equipment aim to overcome shortcomings of existing methods for preparing diazomethane and are short in process route, low in raw material cost and high in yield, preparation procedures are safe and environmental friendly, and effects of industrial continuous production can be realized; the method for preparing the diazomethane is implemented by the aid of the equipment, the diazomethane can be generated from a N-methyl-N-nitroso material and alkali metal hydroxide by means of completely closed reaction, stable organic solution can be formed by means of timely extraction by the aid of extraction agents, accordingly, the retention time of the diazomethane in water can be shortened, the decomposition rate of the diazomethane which can generate methyl alcohol and nitrogen when in water can be reduced, the diazomethane yield can be increased, and safety risks of operator poisoning and explosion due to leakage of gaseous diazomethane can be prevented.

Method and equipment for preparing diazomethane

The invention relates to a preparation method of a tapentadol intermediate. A compound with a simple structure is taken as a raw reaction material to prepare 3-(dimethyl amino)-1-(3-methoxyphenyl)-2-methyl-1-acetone which is a tapentadol intermediate. The preparation method is mild in reaction condition, available in raw materials, high in yield of target products, and what's more, super high in product purity.

He Hong

Papers

Method and equipment for preparing diazomethane

Preparation method of tapentadol intermediate