76704-05-7

Basic information

• Product Name: (-)-Corey Lactone Diol
• Synonyms: (3AS,4R,5S,6AR)-(+)-HEXAHYDRO-5-HYDROXY-4-(HYDROXYMETHYL)-2H-CYCLO-PENTA[B]FURAN-2-ONE;(3as,4R,5S,6ar)-(+)-hexahydro-5-hydroxy-4-hoch2-2;(3AS,4R,5S,6AR)-(+)-HEXAHYDRO-5-HYDROXY- 4-HOCH2-2H-CYCLOPENTA(B)FURAN-2-ONE, 98%;2H-Cyclopenta[b]furan-2-one,hexahydro-5-hydroxy-4-(hydroxymethyl)-,(3aS,4R,5S,6aR)-;(3aR,4S,5R,6aS)-5-hydroxy-4-(hydroxyMethyl)-hexahydrocyclopenta[b]furan-2-one;(3aS,4R,5S,6aR)-5-Hydroxy-4-(hydroxyMethyl)hexahydro-2H-cyclopenta[b]furan-2-one;(3aR,5R,6R,6aS)-6-hydroxy-5-(hydroxymethyl)hexahydro-2H-cyclopenta[b]furan-2-one;(3aS,4R,5S,6aR)-(+)-Hexahydro-5-hydroxy-4-(hydroxymethyl)-2H-cyclopenta[b]furan-2-one 98%
• CAS NO: 76704-05-7
• Molecular Formula: C₈H₁₂O₄
• Molecular Weight: 172.18
• Mol File: 76704-05-7.mol

Chemical Properties

• Melting Point: 114-118 °C(lit.)
• Boiling Point: 406.62 °C at 760 mmHg
• Flash Point: 172.938 °C
• Appearance: /
• Density: 1.365
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.546
• Storage Temp.: 2-8°C
• PKA: 14.36±0.40(Predicted)
• CAS DataBase Reference: (-)-Corey Lactone Diol(CAS DataBase Reference)
• NIST Chemistry Reference: (-)-Corey Lactone Diol(76704-05-7)
• EPA Substance Registry System: (-)-Corey Lactone Diol(76704-05-7)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 76704-05-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(-)-Corey Lactone Diol is used as an impurity in Bimatoprost, an antiglaucoma agent, for the treatment of glaucoma and ocular hypertension. It is important to monitor and control the levels of this impurity to ensure the safety and efficacy of the drug.

InChI:InChI=1/C8H12O4/c9-3-5-4-1-8(11)12-7(4)2-6(5)10/h4-7,9-10H,1-3H2/t4-,5-,6-,7+/m0/s1

Upstream product

• 50-00-0 formaldehyd 
• 34638-25-0 (1R,5S)-2-oxabicyclo[3.3.0]oct-6-en-3-one 
• 108-05-4 vinyl acetate 
• 54423-47-1 (+/-)-(3aα,4α,5β,6aα)-5-hydroxy-4-(hydroxymethyl)hexahydro-2H-cyclopentafuran-2-one 
• 90529-18-3 (1SR, 5RS, 6RS, 7RS)-7-acetoxy-6-acetoxymethyl-2-oxabicyclo<3.3.0>octan-3-one 
• 51705-34-1 2-oxa-3-oxo-6-syn-hydroxymethyl-7-anti-acetoxy-cis-bicyclo[3,3,0]octane 
• 134732-93-7 2-oxa-3-oxo-6-syn-acetoxymethyl-7-anti-hydroxy-cis-bicyclo[3,3,0]octane 
• 110-87-2 3,4-dihydro-2H-pyran 
• 197523-89-0 (3aS,4R,5S,6aR)-4-(tert-Butyl-dimethyl-silanyloxymethyl)-5-(tetrahydro-pyran-2-yloxy)-hexahydro-cyclopenta[b]furan-2-one 
• 107796-38-3 Acetic acid (3aS,4R,5S,6aR)-4-acetoxymethyl-2-oxo-hexahydro-cyclopenta[b]furan-5-yl ester 
• 71155-04-9 (1S,5R)-(-)-bicyclo[3.2.0]hept-2-en-6-one 
• 107437-57-0 exo-(1S,5R,6R)-bicyclo[3.2.0]hept-2-en-6-ol 
• 13173-09-6 bicyclo[3.2.0]hept-2-en-6-one 
• 5307-99-3 7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one 

Downstream Products

• 105394-12-5 Toluene-4-sulfonic acid (3aS,5S,6aR)-5-hydroxy-2-oxo-hexahydro-cyclopenta[b]furan-4-ylmethyl ester 
• 86021-78-5 (3aS,5S,6aR)-4-Phenylsulfanylmethyl-hexahydro-cyclopenta[b]furan-2,5-diol 
• 86021-69-4 (3aS,5S,6aR)-5-Hydroxy-4-phenylsulfanylmethyl-hexahydro-cyclopenta[b]furan-2-one 
• 105394-13-6 (3aR,5R,6aS)-2-Methoxy-4-phenylsulfanylmethyl-hexahydro-cyclopenta[b]furan-5-ol 
• 105394-14-7 tert-Butyl-((3aS,5S,6aR)-2-methoxy-4-phenylsulfanylmethyl-hexahydro-cyclopenta[b]furan-5-yloxy)-dimethyl-silane 
• 105394-06-7 1-Benzenesulfonyl-1-[(3aS,5S,6aR)-5-(tert-butyl-dimethyl-silanyloxy)-2-methoxy-hexahydro-cyclopenta[b]furan-4-yl]-heptan-2-ol 
• 105394-08-9 2-Benzenesulfonyl-2-[(3aS,5S,6aR)-5-(tert-butyl-dimethyl-silanyloxy)-2-methoxy-hexahydro-cyclopenta[b]furan-4-yl]-1-phenyl-ethanol 
• 105394-07-8 2-Benzenesulfonyl-2-[(3aS,5S,6aR)-5-(tert-butyl-dimethyl-silanyloxy)-2-methoxy-hexahydro-cyclopenta[b]furan-4-yl]-1-(2,2-dimethyl-[1,3]dioxolan-4-yl)-ethanol 
• 105394-05-6 1-Benzenesulfonyl-3-(tert-butyl-dimethyl-silanyloxy)-1-[(3aS,5S,6aR)-5-(tert-butyl-dimethyl-silanyloxy)-2-methoxy-hexahydro-cyclopenta[b]furan-4-yl]-octan-2-ol 
• 105394-11-4 tert-Butyl-[(2S,3aS,5S,6aR)-2-methoxy-4-((E)-styryl)-hexahydro-cyclopenta[b]furan-5-yloxy]-dimethyl-silane 
• 551-11-1 (Z)-7-[(3R,5S)-3,5-Dihydroxy-2-((E)-(R)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid 
• 105394-04-5 ((2S,3aS,5S,6aR)-4-Benzenesulfonylmethyl-2-methoxy-hexahydro-cyclopenta[b]furan-5-yloxy)-tert-butyl-dimethyl-silane 
• 105394-04-5 ((2R,3aS,5S,6aR)-4-Benzenesulfonylmethyl-2-methoxy-hexahydro-cyclopenta[b]furan-5-yloxy)-tert-butyl-dimethyl-silane 
• 114826-79-8 (3aS,4R,5S,6aR)-5-Benzyloxy-4-benzyloxymethyl-hexahydro-cyclopenta[b]furan-2-one 

Relevant articles and documents

Novel preparation method and intermediates of entecavir

The invention provides novel intermediates used for entecavir synthesis, compounds shown as a formula II and a formula III in the description, and a novel method for synthesizing entecavir by using the novel intermediates. When the novel intermediates are used for synthesizing entecavir, not only can the synthesis yield be remarkably improved, but also the production cost can be reduced.

Improved entecavir intermediate synthesis process and improved entecavir synthesis process

The invention discloses an improved entecavir intermediate synthesis process and an improved entecavir synthesis process, and relates to the technical field of drug synthesis. The invention disclosesan improved entecavir intermediate synthesis process. In the synthesis process of an amino protection reaction product, amino protecting groups are added in batches; and the ratio of the reaction rawmaterials is optimized, so that the problems of long reaction time and relatively low amino protection reaction yield due to adoption of a one-time complete feeding mode in an existing synthesis modeare solved, the synthesis time of an amino protection reaction product is shortened to 50-70 minutes, and the obtained product is high in yield and purity. According to the improved entecavir synthesis process, in the amino protection reaction product synthesis process, reaction conditions are effectively optimized, and the purity of obtained entecavir reaches 99% or above.

Entecavir intermediate and synthesis method thereof as well as method for synthesis of entecavir

The invention relates to an entecavir intermediate and a preparation method thereof and a method for synthesis of entecavir by using the intermediate. The methods for synthesis of the entecavir and the entecavir intermediate have the advantages of controllable chirality, high yield and high product purity, raw materials are wide in source, reagents are cheap and easily available, the reaction is simple, the operation is simple and convenient, green and environment-friendly effects are achieved, and the method is suitable for industrial large-scale production.

Method for synthesizing entecavir

The invention provides a method for synthesizing entecavir. The method comprises the steps of carrying out condensation ring-closure reaction, bromination addition reaction, reduction reaction, Witting reaction and the like. The method has the beneficial effects that the reaction raw material is easy to obtain, the reaction process is simple in operation, the requirement on reaction equipment is low, the reaction condition is relatively mild and the yield and the content are high.

HPLC and SFC enantioseparation of (±)-Corey lactone diol: Impact of the amylose tris-(3,5-dimethylphenylcarbamate) coating amount on chiral preparation

As an important intermediate of prostaglandins and entecavir, optically pure Corey lactone diol (CLD) has great value in the pharmaceutical industry. In this work, the enantioseparation of (±)-CLD was evaluated using high-performance liquid (HPLC) and supercritical fluid chromatography (SFC). In HPLC, the separations of CLD enantiomers on polysaccharide-based chiral stationary phases with both normal phase and polar organic phase were screened. And the conditions for the enantioseparation were optimized in HPLC and SFC, including the selection of mobile phase, temperature, back-pressure, and other conditions. More important, it was found that the chiral resolutions were greatly enhanced by the increase of the coating amount of ADMPC (amylose tris-(3,5-dimethylphenylcarbamate)) under both HPLC and SFC conditions, which can lead to the increase of the productivity and the decrease of the solvent consumption. The preparations of optically pure CLD were evaluated on a semi-preparative (2?×?25?cm) column packed with 30% ADMPC-coated CSP under HPLC and SFC conditions. Preparative performances in terms of kkd are 1.536?kg racemate/kg CSP/day and 1.248?kg racemate/kg CSP/day in HPLC and SFC, respectively.

A new scalable synthesis of entecavir

A new synthesis of entecavir from D-glucose in an average total yield of 3.5% was achieved via an intramolecular nitrile oxide cycloaddition (INOC) reaction and a Peterson olefination as key-steps. The present process was designed for industrial application, using widely available raw materials, simple and cheap reagents and avoiding low reaction temperatures, which are very common in the synthetic approaches towards similarly complex structures.

Total Synthesis of Entecavir: A Robust Route for Pilot Production

A practical synthetic route for pilot production of entecavir is described. It is safe, robust, and scalable to kilogram scale. Starting from (S)-(+)-carvone, this synthetic route consists of a series of highly efficient reactions including a Favorskii rearrangement-elimination-epimerization sequence to establish the cyclopentene skeleton, the Baeyer-Villiger oxidation/rearrangement to afford the correct configuration of the secondary alcohol, and a directed homoallylic epoxidation followed by epoxide ring-opening to introduce the hydroxyl group suitable for the Mitsunobu reaction. In addition, the synthesis contains only four brief chromatographic purifications.

Entecavir industrial preparation method (by machine translation)

The invention discloses entecavir industrial preparation method, which belongs to the technical field of organic synthesis. Including: Nysted reagent and intermediate VIII reaction, after the reaction is finished adding quenching fluid and holding the reaction system pH value of 7.0 - 8.5, obtained after the completion of reaction intermediates IX; intermediate IX react with hydrochloric acid, after the reaction is finished by adding the extractant and adjust pH value to 6.5 - 7.0, taking organic phase concentrated to 1/15 - 1/10 volume, crystallization, solid-liquid separation to obtain the intermediate X; intermediate with boron trichloride in dichloromethane in the X reaction, intermediate X with boron trichloride in a molar ratio of 1:5 - 10, the reaction temperature is - 30 — - 20 °C, after the reaction is finished cooling to - 30 °C following, dripping methanol, after the completion of the dropping the evaporation and once again by adding methanol, concentrated under reduced pressure, dryness and add into the water with the organic solvent of the extractant B, [...], adjust pH value to 6.5 - 7.0, concentrated, refine to get entecavir. (by machine translation)

Entecavir intermediate and its preparation method

The invention discloses an entecavir intermediate and a preparation method thereof. A provided preparation method for an entecavir intermediate compound 8 comprises the following steps: performing hydroxyl protection group removal reaction on a compound 9 in a solvent under an acidic condition, so as to obtain the compound 8. A provided preparation method for an entecavir intermediate compound 9 comprises the following steps: performing hydroxyl protection group adding reaction on a compound 10 in an aprotic organic solvent under an alkali condition, so as to obtain the compound 9. The preparation methods are cheap and easily available in raw materials, mild in reaction conditions, relatively high in product yield, good in atom economy, friendly to environment, and suitable for industrialized production.

Entecavir intermediate and its preparation method

The invention discloses an entecavir intermediate and a preparation method thereof. A provided preparation method for an entecavir intermediate compound 3 comprises the following steps: performing reducing reaction on a compound 4 in a solvent, so as to obtain the compound 3. A provided preparation method for an entecavir intermediate compound 4 comprises the following steps: performing transacetalation reaction on a compound 5 and a compound 18 in an organic solvent under an acid condition, so as to obtain the compound 4. The preparation methods are cheap and easily available in raw materials, mild in reaction conditions, relatively high in product yield, good in atom economy, friendly to environment, and suitable for industrialized production.