Chemical Development of a Pilot Scale Process for the ACAT Inhibitor 2,6-Diisopropylphenyl [(2,4,6-Triisopropylphenyl)acetyl]sulfamate

Autor:	Gary J. Dozeman, Phillip J. Fiore, and Timothy P. Puls, Walker Jonathan
Rok vydání:	1997
Předmět:	Sulfonyl chemistry.chemical_classification Chlorosulfonyl isocyanate Chemistry Decarboxylation Organic Chemistry Convergent synthesis Cyanation Chloride Medicinal chemistry Isocyanate chemistry.chemical_compound Acetyl chloride medicine Physical and Theoretical Chemistry medicine.drug
Zdroj:	Organic Process Research & Development. 1:137-148
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op9600419
Popis:	A manufacturing process to prepare the ACAT inhibitor 2,6-diisopropylphenyl [(2,4,6-triisopropylphenyl)acetyl]sulfamate (1; CI-1011) has been developed and successfully demonstrated on a pilot scale. Commercially available 1,3,5-triisopropylbenzene (9) was chloromethylated to give 2,4,6-triisopropylbenzyl chloride (8). Cyanation of 8 under phase-transfer-catalyzed conditions followed by basic hydrolysis of the intermediate and nonisolated 2,4,6-triisopropylbenzyl cyanide (7) gave 2,4,6-triisopropylphenylacetic acid (2), a key intermediate in the convergent synthesis of 1. Commercially available 2,6-diisopropylphenol (12) was converted to [(2,6-diisopropylphenyl)oxy]sulfonyl isocyanate (13) when reacted with chlorosulfonyl isocyanate under thermodynamically controlled conditions. Hydrolysis and decarboxylation of 13 in situ gave 2,6-diisopropylphenyl sulfamate (3), the other key intermediate. A robust process to couple 2 and 3 was developed via the intermediacy of (2,4,6-triisopropylphenyl)acetyl chloride ...
Databáze:	OpenAIRE
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