204254-90-0

Basic information

• Product Name: (3aR,7R,7aR)-2,2-Diethyl-3a,6,7,7a-tetrahydro-7-[(Methylsulfonyl)oxy]-1,3-benzodioxole-5-carboxylic Acid Ethyl Ester
• Synonyms: (3aR,7R,7aR)-2,2-Diethyl-3a,6,7,7a-tetrahydro-7-[(Methylsulfonyl)oxy]-1,3-benzodioxole-5-carboxylic Acid Ethyl Ester
• CAS NO: 204254-90-0
• Molecular Formula: C₁₅H₂₄O₇S
• Molecular Weight: 348.41186
• Mol File: 204254-90-0.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 474.211°C at 760 mmHg
• Flash Point: 240.594°C
• Appearance: /
• Density: 1.267g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.515
• Storage Temp.: Hygroscopic, Refrigerator, under inert atmosphere
• Solubility: Chloroform (Sparingly), Ethyl Acetate (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (3aR,7R,7aR)-2,2-Diethyl-3a,6,7,7a-tetrahydro-7-[(Methylsulfonyl)oxy]-1,3-benzodioxole-5-carboxylic Acid Ethyl Ester(CAS DataBase Reference)
• NIST Chemistry Reference: (3aR,7R,7aR)-2,2-Diethyl-3a,6,7,7a-tetrahydro-7-[(Methylsulfonyl)oxy]-1,3-benzodioxole-5-carboxylic Acid Ethyl Ester(204254-90-0)
• EPA Substance Registry System: (3aR,7R,7aR)-2,2-Diethyl-3a,6,7,7a-tetrahydro-7-[(Methylsulfonyl)oxy]-1,3-benzodioxole-5-carboxylic Acid Ethyl Ester(204254-90-0)

Safety Data

• Hazardous Substances Data: 204254-90-0(Hazardous Substances Data)

Usage

Uses

(3aR,7R,7aR)-2,2-Diethyl-3a,6,7,7a-tetrahydro-7-[(methylsulfonyl)oxy]-1,3-benzodioxole-5-carboxylic Acid Ethyl Ester is an analog of (1R,5S,6S)-rel-5-(1-Ethylpropoxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic Acid Methyl Ester (E925665) which is an intermediate in the synthesis of neuraminidase inhibitors.

InChI:InChI=1/C15H24O7S/c1-5-15(6-2)20-11-8-10(14(16)19-7-3)9-12(13(11)21-15)22-23(4,17)18/h8,11-13H,5-7,9H2,1-4H3/t11-,12-,13-/m1/s1

Upstream product

• 943515-58-0 (3aR,7R,7aS)-ethyl 2,2-diethyl-7-hydroxy-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-carboxylate 
• 124-63-0 methanesulfonyl chloride 
• 77-95-2 D-(-)-quinic acid 
• 136994-78-0 ethyl (3aR,7R,7aS)-2,2-dimethyl-7-hydroxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate 
• 32384-42-2 (1S,3R,4S,5R)-3,4-O-isopropylidene-1,5-quinic lactone 
• 77-76-9 2,2-dimethoxy-propane 
• 204254-81-9 ethyl (3aR,5S,7R,7aR)-5-hydroxy-7-methanesulfonyloxy-2,2-dimethylhexahydrobenzo[1,3]dioxole-5-carboxylate 
• 96-22-0 pentan-3-one 
• 204254-84-2 ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate 
• 138-59-0 shikimic acid 
• 101769-63-5 (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid ethyl ester 

Downstream Products

• 204254-92-2 ethyl (3R,4R,5R)-3-(1-ethyl-propoxy)-4-hydroxy-5-methanesulfonyloxycyclohex-1-ene-1-carboxylate 
• 204255-00-5 ethyl (3R,4S,5R)-4-azido-3-(1-ethylpropoxy)-5-hydroxy-1-cyclohexene-1-carboxylate 
• 204254-98-8 ethyl-(3R,4S,5R)-5-azido-4-hydroxy-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate 
• 196618-13-0 oseltamivir 
• 204255-09-4 oseltamivir hydrochloride 
• 204255-11-8 oseltamivir phosphate 
• 204255-02-7 ethyl-(1R,5R,6R)-5-(pentan-3-yloxy)-7-azabicyclo[4.1.0]hept-3-ene-3-carboxylate 
• 204255-06-1 oseltamivir 
• 204255-04-9 ethyl-(3R,4R,5S)-4-amino-5-azido-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate 
• 204254-96-6 (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester 

Relevant articles and documents

Crystallization method of intermediate 5 of high-purity oseltamivir phosphate

5 (Pentane 5 -yloxy) -3 - oxo -7 - bicyclo [-] hep 4.1.0-3 -3 - carboxylate ethyl carboxylate is concentrated to precipitate crystals, and then crystals are directly put into a mixed solvent composed of an alkane solvent and an alcohol solvent. Through the crystallization method, the purity of the intermediate 5 can reach above 99.7%, and the requirement for preparing oseltamivir phosphate is completely met.

Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus

Evidences of oseltamivir resistant influenza patients raised the need of novel neuraminidase inhibitors. In this study, five oseltamivir analogs PMC-31-PMC-36, synthesised according to the outcomes of a rational design analysis aimed to investigate the effects of substitution at the 5-amino and 4-amido groups of oseltamivir on its antiviral activity, were screened for their inhibition against neuraminidase N1 and N3. The enzymes used as models were from the avian influenza A H7N1 and H7N3 viruses. The neuraminidase inhibition assay was carried out by using recombinant species obtained from a baculovirus expression system and the fluorogenic substrate MUNANA. The assay was validated by using oseltamivir carboxylate as a reference inhibitor. Among the tested compounds, PMC-36 showed the highest inhibition on N1 with an IC50 of 14.6 ± 3.0 nM (oseltamivir 25 ± 4 nM), while PMC-35 showed a significant inhibitory effect on N3 with an IC50 of 0.1 ± 0.03 nM (oseltamivir 0.2 ± 0.02 nM). The analysis of the inhibitory properties of this panel of compounds allowed a preliminary assessment of a structure-activity relationship for the modification of the 4-amido and 5-amino groups of oseltamivir carboxylate. The substitution of the acetamido group in the oseltamivir structure with a 2-butenylamido moiety reduced the observed activity, while the introduction of a propenylamido group was well tolerated. Substitution of the free 5-amino group of oseltamivir carboxylate with an azide, decreased the activity against both N1 and N3. When these structural changes were both introduced, a dramatic reduction of activity was observed for both N1 and N3. The alkylation of the free 5-amino group in oseltamivir carboxylate introducing an isopropyl group seemed to increase the inhibitory effect for both N1 and N3 neuraminidases, displaying a more pronounced effect against N1.

Industrial synthesis of the key precursor in the synthesis of the anti-influenza drug oseltamivir phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1 -ene-1 -carboxylate

Starting from (-)-quinic acid, the title compound was synthesized in seven chemical steps and an overall yield of 35-38%. The route of the improved Gilead synthesis was not changed. However, significant improvements in each step led to a doubled overall yield, a 30% reduction in the number of unit operations, and an excellent quality (≥99%) of the resulting epoxide. A highly regioselective method for the dehydration of a quinic acid to a shikimic acid derivative and for the reduction of a cyclic ketal was found. Alternatively, the title compound was synthesized in six chemical steps and 63-65% yield from commercially available (-)-shikimic acid. Compared to the optimized quinic acid route, the production time was reduced by about 50%. The quality of epoxide produced from either natural product was equivalent. Therefore (-)-shikimic acid is the preferred raw material. The absolute configuration of the epoxide was determined by X-ray single crystal structure analysis and it was demonstrated that the epoxide was stereo-isomerically pure.