Synlett 2017; 28(17): 2330-2334
DOI: 10.1055/s-0036-1588484
letter
© Georg Thieme Verlag Stuttgart · New York

Scalable Synthesis of 6,6-Dimethylbicyclo[3.1.0]hexan-3-one

Steven M. Mennen*a, Athimoolam Arunachalampillaib, Deborah M. Choquettea, Harikrishna Muppallab, Krishna Sheenab
  • aProcess Development, Amgen, Inc., 360 Binney Street, Cambridge, Massachusetts 02142, USA   Email: smennen@amgen.com
  • bChemical Development, Syngene Intl. Ltd., Biocon Park, Plot No. 2 & 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India
Further Information

Publication History

Received: 26 April 2017

Accepted after revision: 02 June 2017

Publication Date:
18 July 2017 (eFirst)

Abstract

A simple five-step process for the conversion of technical grade (+)-3-carene into 6,6-dimethylbicyclo[3.1.0]hexan-3-one was developed. A robust process was required that delivered the 6,6-dimethylbicyclo[3.1.0]hexan-3-one, minimized chromatography, reduced the excess of silver salts, and avoided toxic chromium oxidants. A simple and scalable process that relies on crystallization and distillation was developed and demonstrated to produce hundreds of grams of 6,6-dimethylbicyclo[3.1.0]hexan-3-one.

Supporting Information