367252-67-3

Basic information

• Product Name: (3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester
• Synonyms: (3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester
• CAS NO: 367252-67-3
• Molecular Weight: 396.487
• Mol File: 367252-67-3.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: (3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester(367252-67-3)
• EPA Substance Registry System: (3R,4R,5S)-4-azido-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethyl ester(367252-67-3)

Safety Data

• Hazardous Substances Data: 367252-67-3(Hazardous Substances Data)

Upstream product

• 1393086-01-5 C₂₅H₃₇O₉P 
• 943515-58-0 (3aR,7R,7aS)-ethyl 2,2-diethyl-7-hydroxy-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-carboxylate 
• 1234287-00-3 ethyl (3R,4S,5S)-3-(1-ethylpropoxy)-4-hydroxy-5-amino-cyclohex-1-ene-1-carboxylate 
• 1234286-93-1 (3aR,7aS)-ethyl 2,2-diethyl-7-(hydroxyimino)-3a,6,7,7a-tetrahydrobenzo[d][1,3]dioxole-5-carboxylate 
• 1234286-95-3 ethyl 3,4-O-isopentylidene-5-oxo shikimate 
• 367252-65-1 (3R,4S,5S)-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)-4-hydroxycyclohex-1-enecarboxylic acid ethyl ester 
• 367252-66-2 (3R,4S,5S)-5-tert-butoxycarbonylamino-3-(1-ethylpropoxy)-4-trifluoromethanesulfonyloxycyclohex-1-enecarboxylic acid ethyl ester 
• 67-64-1 acetone 

Downstream Products

• 367252-68-4 (3R,4R,5S)-ethyl 4-acetamido-5-((tert-butoxycarbonyl)amino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 
• 204255-11-8 oseltamivir phosphate 
• 1012814-35-5 (3R,4R,5S)-ethyl 4-amino-5-(tert-butoxycarbonylamino)-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate 

Relevant articles and documents

A concise and practical synthesis of oseltamivir phosphate(Tamiflu) from d-mannose

A short and practical synthesis of oseltamivir phosphate was accomplished in 11 steps from inexpensive and abundant starting material, d-mannose. This synthetic route featured an intramolecular Horner-Wadsworth-Emmons reaction as the key step to furnish the cyclohexene ring product. The hydroxyl group was converted stereo specifically into an amino group by oxidation to the ketone and reductive amination whereas the second amino group was introduced by azide substitution of a hydroxyl group. This synthesis provided an economical and practical alternative for the synthesis of Tamiflu.

New, efficient synthesis of oseltamivir phosphate (Tamiflu) via enzymatic desymmetrization of a meso-1,3-cyclohexanedicarboxylic acid diester

(Chemical Equation Presented) A new, enantioselective synthesis of the influenza neuraminidase inhibitor prodrug oseltamivir phosphate 1 (Tamiflu) and its enantiomer ent-1 starting from cheap, commercially available 2,6-dimethoxyphenol 10 is described. The main features of this approach comprise the cis-hydrogenation of 5-(1-ethyl-propoxy)-4,6-dimethoxy-isophthalic acid diethyl ester (6a) and the desymmetrization of the resultant all-cis meso-diesters 7a and 7b, respectively. Enzymatic hydrolysis of the meso-diester 7b with pig liver esterase afforded the (S)-monoacid 8b, which was converted into cyclohexenol 17 via a Curtius degradation and a base-catalyzed decarboxylative elimination of the Boc-protected oxazolidinone 14. Introduction of the second amino function via SN2 substitution of the corresponding triflate 18 with NaN3 followed by azide reduction, N-acetylation, and Boc-deprotection gave oseltamivir phosphate 1 in a total of 10 steps and an overall yield of ～30%. The enantiomer ent-1 was similarly obtained via an enzymatic desymmetrization of meso-diester 7a with Aspergillus oryzae lipase, providing the (R)-monoacid ent-8a.