637-75-2

Upstream product

• 74-90-8 hydrogen cyanide 
• 151-50-8 potassium cyanide 
• 106-89-8 epichlorohydrin 
• 143-33-9 sodium cyanide 
• 109-75-1 but-3-enenitrile 
• 135908-05-3 2-hydroxy-3-chloropropyl p-toluenesulfonate 
• 128993-20-4 3-Bromo-5-chloromethyl-4,5-dihydro-isoxazole 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 7677-24-9 trimethylsilyl cyanide 
• 773837-37-9 sodium cyanide 
• 95548-93-9 (S)-2-Acetoxy-1-bromo-3-chloropropane 
• 96-23-1 1,3-Dichloro-2-propanol 
• 146864-18-8 (R)-4-chloromethyl-[1,3,2]dioxathiolane 2-oxide 
• 105-33-9 4-chloro-3-hydroxybutyronitrile 

Downstream Products

• 10479-81-9 (2E)-4-hydroxybut-2-enenitrile 
• 13880-89-2 3-hydroxyglutaronitrile 
• 19060-14-1 γ-Cyano-allylalkohol 
• 7659-46-3 4-chloro-trans-crotononitrile 
• 10488-68-3 methyl 4-chloro-3-hydroxybutanoate 
• 624-58-8 3,4-epoxybutanenitrile 
• 1116-95-6 (D)-(+)-carnitinenitrile chloride 
• 727382-14-1 (3S)-4-chloro-3-[(trimethylsilyl)oxy]butyronitrile 
• 100243-39-8 3-hydroxypyrrolidine 

Relevant academic research and scientific papers

Method for synthesizing high-content (S)-4-chloro-3-hydroxybutyronitrile

The invention relates to a method for synthesizing high-content (S)-4-chloro-3-hydroxybutyronitrile. The method comprises the following step: by taking S-type epoxy chloropropane as a reaction substrate and trimethylsilyl cyanide as a cyaniding agent in the presence of water, obtaining the (S)-4-chloro-3-hydroxybutyronitrile. According to the invention, traditional sodium cyanide or hydrogen cyanide is not used as a cyaniding agent, so that potential safety hazards in production are avoided, harsh production conditions are not needed, cyanide-containing wastewater is not generated, the wastewater treatment cost of enterprises is reduced, side reactions are reduced, the yield of target products is increased, and the subsequent purification difficulty is reduced; and the method further optimizes the molar ratio of the catalyst to the reaction substrate to the cyaniding agent to water to the catalyst, the reaction time, the reaction temperature and other conditions so as to further reduce the probability of side reaction, and improve the yield and the purity of the product.

A Cyanide-free Biocatalytic Process for Synthesis of Complementary Enantiomers of 4-Chloro-3-hydroxybutanenitrile From Allyl Chloride

A biocatalyst used for selective ring scission of (±)-5-(chloromethyl)-4, 5-dihydroisoxazole to synthesize chiral (R)-4-chloro-3-hydroxybutanenitrile (90 % ee, 39 % isolated yield) and (S)-5-(chloromethyl)-4, 5-dihydroisoxazole (99 % ee, 39 % isolated yield) was developed by site-saturated mutagenesis on aldoxime dehydratase derived from Pseudomonas chlororaphis B23 (OxdA). The positive mutant (OxdA-L318I, E=68) improved the enantiomeric ratio E by 6-fold as compared to the wild type enzyme (OxdA-wild, E=11). The racemic precursor of (±)-5-(chloromethyl)-4, 5-dihydroisoxazole, used in the reaction, can be synthesized from readily available allyl chloride without utilizing highly toxic cyanide. The enantiopure (S)-5-(chloromethyl)-4, 5-dihydroisoxazole remaining in the kinetic resolution can be transformed into corresponding chiral (S)-4-chloro-3-hydroxybutanenitrile without loss of enantiomeric excess by treating it with triethylamine in acetonitrile (99 % ee, 72 % isolated yield) or catalysis of OxdA-wild enzyme (99 % ee, 88 % isolated yield).

Preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as starting material

The invention discloses a preparation method for synthesizing L-carnitine by using R-(-)-epichlorohydrin as a starting material, and belongs to the field of medicinal chemistry. The method comprises the steps: using R-(-)-epoxychlorohydrin and hydrocyanic acid as starting materials, performing a reaction for synthesis of R-4-chloro-3-hydroxybutyronitrile under the action of a basic catalyst, thensynthesizing L-carnitine hydrochloride through two routes, purifying the L-carnitine hydrochloride prepared through the two routes further through resin so as to remove chloride ions, and preparing the final product L-carnitine. The two process routes are simple, the reaction conditions are mild, the operation is simple and feasible, and industrial production is convenient; the whole process is green and environmentally friendly, the reaction yield is high, three waste is little, no sodium cyanide is used, and no solid waste sodium salt is generated; and the hydrolysis by-product ammonium chloride has good quality, and can be sold as a by-product, and great economic benefits and market competitiveness are achieved.

Synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine

The invention discloses a synthesis method of L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine. The synthesis method is characterized in that: (R)-epichlorohydrin serves as a starting material; the (R)-epichlorohydrin is firstly subjected to a ring-opening reaction by gaseous hydrogen cyanide; L-(-)-4-chlorine-3-hydroxybutyronitrile is obtained; then the L-(-)-4-chlorine-3-hydroxybutyronitrile is aminated by trimethylamine; and the L-(-)-chlorination 3-cyano-2-propyltrimethylamine is obtained. After the ring-opening reaction is completed, a small amount of hydrogen cyanide dissolved in a material needs to be replaced with nitrogen, and an end point is that a benzidine-cupric acetate test paper does not change to blue. According to the synthesis method, thegaseous hydrogen cyanide is firstly used to open a ring, and then the trimethylamine is used to perform amination, therefore the L-carnitine intermediate L-(-)-chlorination 3-cyano-2-hydroxypropyltrimethylamine with high yield and high content can be obtained; and by adopting the gaseous hydrogen cyanide to open the ring, only the nitrogen is needed to replace the gaseous hydrogen cyanide after the ring-opening reaction, the subsequent recovery of the trimethylamine is not affected, and the post-treatment process is greatly simplified.

Method for synthesizing butyrolactone derivative

The invention discloses a method for synthesizing a butyrolactone derivative. The method comprises steps as follows: (1), after being activated by a titanium reagent, an epoxy compound represented asa formula (II) is subjected to an addition reaction by a Grignard reagent, and a compound represented as a formula (III) is obtained; (2), the compound represented as the formula (III) is subjected tocyano hydrolysis under the alkaline condition, and a carboxylic acid derivative represented as a formula (IV) is obtained; (3), the carboxylic acid derivative represented as the formula (IV) is subjected to a dehydration cyclization reaction, and the butyrolactone derivative represented as a formula (I) is obtained. The method has the advantages of being simple in synthesis step, low in production cost and high in functional group selectivity, regioselectivity and yield; the synthetic route is shown in the description.

Preparation method of 1-BOC-3-hydroxymethyl pyrrolidine

The invention discloses a preparation method of 1-Boc-3-hydroxymethyl pyrrolidine. The preparation method uses epichlorohydrin as a raw material, 3-hydroxymethyl pyrrolidine is obtained through reduction and cyclization reaction, then the 1-Boc-3-hydroxymethyl pyrrolidine is prepared through Boc protection reaction, then 1-BOC-3-methyl formate pyrrolidine is prepared through carboxylation reaction and esterification reaction, and finally the 1-BOC-3-methyl formate pyrrolidine and lithium aluminum hydride are catalyzed by a catalyst to prepare the 1-BOC-3-hydroxymethyl pyrrolidine. The preparation method is high in product synthesis rate, high in product purity and low in production cost, and the raw materials are cheap and easy to obtain.

A One-Step Biocatalytic Process for (S)-4-Chloro-3-hydroxybutyronitrile using Halohydrin Dehalogenase: A Chiral Building Block for Atorvastatin

(S)-4-Chloro-3-hydroxybutyronitrile [(S)-CHBN] was used as a chiral building block for the preparation of atorvastatin. In this study, (R,S)-epichlorohydrin [(R,S)-ECH] and 1,3-dichloro-2-propanol (1,3-DCP) were investigated to prepare (S)-CHBN by using the halohydrin dehalogenase HheC from Agrobacterium radiobacter AD1. Preparing (S)-CHBN from (R,S)-ECH gave a modest enantiomeric excess (ee), whereas by using 1,3-DCP as the substrate, (S)-CHBN was obtained with 97.3 % ee after pH optimization. However, a low ee value and low yield of (S)-CHBN were obtained if the substrate concentration was increased to 10 g L-1. To obtain a higher ee value and yield, 16 mutants were constructed and screened. The variant W249F with improvements in activity and enantioselectivity was identified and applied at a 1,3-DCP loading of 10 g L-1, which gave (S)-CHBN in 86 % yield with 97.5 % ee in 1 h. This is the first report of a one-step biocatalytic process for the preparation of (S)-CHBN from prochiral 1,3-DCP.

A new practical synthesis of ethyl (R)-(-)-4-Cyano-3-hydroxybutyrate from (S)-3-chloro-1,2-propanediol

A practical chemical synthesis of ethyl (R)-(-)-4-Cyano-3- hydroxybutyrate((R)-CNHB) has been accomplished from (S)-3-chloro-1,2- propanediol, which is a main by-product originating from (S,S)-Salen Co(III) catalyzed by hydrolytic kinetic resolution (HKR) of epichlorohydrin. The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of the intermediate of atorvastatin.

Asymmetric synthesis of l-carnitine from (R)-3-chloro-1,2-propanediol

A practical chemical synthesis of l-carnitine (1) has been accomplished from (R)-3-chloro-1,2-propanediol ((R)-4), which is a main by-product originated from (R,R)-Salen Co(III) catalyzed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin. (R)-4 was utilized as a chiral starting material to prepare the key intermediate cyclic sulfite ((R)-5). The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of bioactive compounds.

Practical and efficient utilisation of (R)-3-chloro-1,2-propanediol in synthesis of L-carnitine

As a by-product originating from Salen Co(III) catalysed hydrolytic kinetic resolution (HKR) of (±)-epichlorohydrin in the manufacturing procedure of L-Carnitine, (R)-3-chloro-1,2-propanediol was utilised as a starting chiral material to prepare via key nitrile intermediates and by a final hydrolysis L-Carnitine. The new synthetic approach demonstrated an efficient utilisation of the by-product.