An efficient conversion of 5-nitroisatin into 5-nitroindole derivative.
Our process research on OPC-35564 revealed that a mixed borohydride reducing agent (ZrCl4/NaBH4) in DME (Itsuno system) afforded a rapid and direct conversion of N-alkyl-nitroisatin into nitroindole nucleus. Comparison with other reducing agents indicated the superiority of the present system and the key function of ZrCl4. For the manipulation of base-labile isatin, a useful procedure for its N-alkylation using Cu2CO3 is also presented.
Torisawa
Y
Y
Process Research Laboratory, Second Tokushima Factory, Otsuka Pharmaceutical Co. Ltd., Japan. torisawa@fact.otsuka.co.jp
Nishi
T
T
Minamikawa
J
J
D000478:Alkylation; D002254:Carbonates / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007510:Isatin / Q000737:chemistry*; D010084:Oxidation-Reduction; D015040:Zirconium / Q000737:chemistry
D002254:Carbonates; D007211:Indoles; D003300:Copper; D007510:Isatin; C086270:copper carbonate; D015040:Zirconium