Process Development of (1S,2S,5R,6S)-Spiro[bicyclo[3.1.0]hexane-2',5'-dioxo-2,4'-imidazolidine]-6-carboxylic Acid, (R)-
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- 作者：Ossama M. Rasmy ; Radhe K. Vaid ; Michael J. Semo ; Erik C. Chelius ; Roger L. Robey ; Charles A. Alt ; Gary A. Rhodes ; and Jeffery T. Vicenzi
- 刊名：Organic Process Research & Development
- 出版年：2006
- 出版时间：January 2006
- 年：2006
- 卷：10
- 期：1
- 页码：28 - 32
- 全文大小：83K
- 年卷期：v.10,no.1(January 2006)
- ISSN：1520-586X
文摘
Process development and a pilot-plant process for the synthesisof 4 and its resolution to obtain (1S,2S,5R,6S)-spiro[bicyclo[3.1.0]hexane-2',5'-dioxo-2,4'-imidazolidine]-6-carboxylic acid,(R)-
-methylbenzenemethanamine salt (5) are described. Starting from the inexpensive raw 2-cyclopenten-1-one and sulfurylide 1 the racemic bicyclo keto ester 2 was synthesized.Reaction of 2 with potassium cyanide and ammonium carbonateunder Bücherer-Berg's reaction conditions affords racemic 3in 80% yield. Hydrolysis of 3 followed by the resolution with(R)-(+)--methylbenzylamine gave 4 in excellent yield andpurity under optimized conditions. The improvement of theoriginal discovery process to accommodate safety and environmental requirements for scale-up in manufacturing facilities isalso discussed.
-methylbenzenemethanamine salt (5) are described. Starting from the inexpensive raw 2-cyclopenten-1-one and sulfurylide 1 the racemic bicyclo keto ester 2 was synthesized.Reaction of 2 with potassium cyanide and ammonium carbonateunder Bücherer-Berg's reaction conditions affords racemic 3in 80% yield. Hydrolysis of 3 followed by the resolution with(R)-(+)--methylbenzylamine gave 4 in excellent yield andpurity under optimized conditions. The improvement of theoriginal discovery process to accommodate safety and environmental requirements for scale-up in manufacturing facilities isalso discussed.