EP 1794177 A2 20070613 - PROCESS FOR PREPARING 7 -ALKOXYCARBONYL SUBSTITUTED STEROIDS
Title (en)
PROCESS FOR PREPARING 7 -ALKOXYCARBONYL SUBSTITUTED STEROIDS
Title (de)
VERFAHREN ZUR HERSTELLUNG VON 7-ALKOXYCARBONYLSUBSTITUIERTEN STEROIDEN
Title (fr)
PROCESSUS DE PREPARATION DE STEROIDES 7-ALCOXYCARBONYLE SUBSTITUE
Publication
Application
Priority
- IB 2005002757 W 20050825
- US 60842504 P 20040909
- US 61213304 P 20040922
Abstract (en)
[origin: WO2006032970A2] Processes are described for the conversion of a steroid substrate having a 4,7-carbonyl bridge to a structure comprising a 7a-alkoxycarbonyl substituent by reaction of the substrate with an alkoxy group source, preferably in the presence of a base. Several optional process modifications are described. The reaction may be conducted at a temperature greater than about 70°C, with substantially shorter residence times than are required at lower temperatures. A saponification target may be incorporated into the reaction medium to consume free hydroxide compounds. The product 7a-alkoxycarbonyl compound may be recovered by crystallization, residual steroid values may be recovered from the crystallization mother liquor by extraction, and the extract may be processed to produce a repulp solution wherein the steroids may be re-equilibrated to produce additional 7a-alkoxycarbonyl substituted steroid product. Alternatively, the repulp solution may be recycled to a primary reactor wherein 4,7-carbonyl bridge substrate is converted to 7a-alkoxycarbonyl product. The process is particularly useful in the preparation of eplerenone, wherein a diketone intermediate comprising a 4,7-carbonyl bridge is reacted with an alkali metal methoxide to yield an 11a-hydroxy-7a-methoxycarbonyl compound (hydroxyester), the 11a-hydroxy group is converted to a leaving group which is then abstracted to produce a ?-9,11 enester, and the enester is epoxidized to eplerenone. Also disclosed is an epoxidation reaction conducted at relatively low hydrogen peroxide to enester substrate ratio.
IPC 8 full level
C07J 53/00 (2006.01); C07J 21/00 (2006.01)
CPC (source: EP)
C07J 21/001 (2013.01); C07J 53/002 (2013.01); Y02P 20/582 (2015.11)
Citation (search report)
See references of WO 2006032970A2
Designated contracting state (EPC)
AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR
DOCDB simple family (publication)
WO 2006032970 A2 20060330; WO 2006032970 A3 20060817; AR 050632 A1 20061108; BR PI0515106 A 20080708; CA 2579954 A1 20060330; EP 1794177 A2 20070613; JP 2008512439 A 20080424; MX 2007002846 A 20070430; TW 200617020 A 20060601
DOCDB simple family (application)
IB 2005002757 W 20050825; AR P050103739 A 20050907; BR PI0515106 A 20050825; CA 2579954 A 20050825; EP 05805074 A 20050825; JP 2007530794 A 20050825; MX 2007002846 A 20050825; TW 94130861 A 20050908