BRPI0515106A - process for preparing substituted 7 (alpha) -alkoxycarbonyl steroids - Google Patents
process for preparing substituted 7 (alpha) -alkoxycarbonyl steroidsInfo
- Publication number
- BRPI0515106A BRPI0515106A BRPI0515106-6A BRPI0515106A BRPI0515106A BR PI0515106 A BRPI0515106 A BR PI0515106A BR PI0515106 A BRPI0515106 A BR PI0515106A BR PI0515106 A BRPI0515106 A BR PI0515106A
- Authority
- BR
- Brazil
- Prior art keywords
- alkoxycarbonyl
- substrate
- steroids
- ester
- steroid
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/001—Lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Abstract
PROCESSO PARA PREPARAR ESTERóIDES 7<244>-ALCOXICARBONIL SUBSTITUìDOS Processos são descritos para a conversão de um substrato esteróide com uma ponte 4,7-carbonil numa estrutura compreendendo um substituinte 7<244>-alcoxicarbonil pela reação do substrato com uma fonte de grupo alcóxi, preferivelmente na presença de uma base. Várias modificações do processo opcionais são descritas. A reação pode ser conduzida numa temperatura maior do que cerca de 70<198>C, com tempos de residência substancialmente mais curtos do que são necessários em temperaturas mais baixas. Um alvo de saponificação pode ser incorporado no meio reacional para consumir compostos de hidróxido livres, O produto composto 7<244>-alcoxicarbonil pode ser recuperado por cristalização, valores de esteróide residuais podem ser recuperados a partir do líquido de origem de cristalização por extração, e o extrato pode ser processado para produzir uma solução novamente reduzida a uma consistência de polpa em que os esteróides podem ser reequilibrados para produzir produto esteróide 7<244>-alcoxicarbonil substituído adicional. Alternativamente, a solução novamente reduzida a uma consistência de polpa pode ser reciclada para um reator primário em que o substrato de ponte 4,7-carbonil é convertido no produto 7<244>-alcoxicarbonil. O processo é particularmente útil no preparo da eplerenona, em que um intermediário dicetona compreendendo uma ponte 4,7-carbonil reage com um metóxido de metal alcalino para produzir um composto 11<244>-hidróxi-7<244>-metoxi-carbonil (hidroxiéster), o grupo 11a-hidróxi é convertido num grupo de saída o qual é, a seguir, abstraído para produzir um enéster <30>¬ 9,11¬m e o enéster é epoxidado em eplerenona. Também revelado é uma reação de epoxidação conduzida numa proporção relativamente baixa de peróxido de hidrogênio em relação ao substrato enéster.Process for Preparing Substituted 7 -244-Alkoxycarbonyl Steroids Processes are described for converting a 4,7-carbonyl bridge steroid substrate into a structure comprising a 7 -24-alkoxycarbonyl substituent by reacting 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 7β-alkoxycarbonyl compound product may be recovered by crystallization, residual steroid values may be recovered from the crystallization source by extraction, and the extract may be processed to produce a solution again reduced to a pulp consistency wherein the steroids may be rebalanced to produce additional substituted 7Î ± -alkoxycarbonyl steroid product. Alternatively, the solution again reduced to a pulp consistency may be recycled to a primary reactor wherein the 4,7-carbonyl bridge substrate is converted to the 7β-alkoxycarbonyl product. The process is particularly useful in the preparation of eplerenone, wherein a diketone intermediate comprising a 4,7-carbonyl bridge reacts with an alkali metal methoxide to produce an 11α-hydroxy-7α-methoxycarbonyl compound ( hydroxyester), the 11α-hydroxy group is converted to an leaving group which is then abstracted to yield an ester <30> 9.11 and the ester is epoxidized to eplerenone. Also disclosed is an epoxidation reaction conducted on a relatively low ratio of hydrogen peroxide to the ester substrate.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60842504P | 2004-09-09 | 2004-09-09 | |
US61213304P | 2004-09-22 | 2004-09-22 | |
PCT/IB2005/002757 WO2006032970A2 (en) | 2004-09-09 | 2005-08-25 | PROCESS FOR PREPARING 7α-ALKOXYCARBONYL SUBSTITUTED STEROIDS |
Publications (1)
Publication Number | Publication Date |
---|---|
BRPI0515106A true BRPI0515106A (en) | 2008-07-08 |
Family
ID=35519906
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BRPI0515106-6A BRPI0515106A (en) | 2004-09-09 | 2005-08-25 | process for preparing substituted 7 (alpha) -alkoxycarbonyl steroids |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP1794177A2 (en) |
JP (1) | JP2008512439A (en) |
AR (1) | AR050632A1 (en) |
BR (1) | BRPI0515106A (en) |
CA (1) | CA2579954A1 (en) |
MX (1) | MX2007002846A (en) |
TW (1) | TW200617020A (en) |
WO (1) | WO2006032970A2 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104262450A (en) * | 2014-09-19 | 2015-01-07 | 江苏嘉逸医药有限公司 | Method for preparing and refining eplerenone |
CN104725461B (en) * | 2015-04-02 | 2016-08-17 | 山东新华制药股份有限公司 | The preparation method of eplerenone |
CN108129536A (en) * | 2017-12-25 | 2018-06-08 | 江西赣亮医药原料有限公司 | A kind of preparation method of Dexamethasone Intermediate |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE787940A (en) * | 1971-08-25 | 1973-02-26 | Searle & Co | NEW DIURETIC AND HYPOTENSIVE MEDICINAL PRODUCTS AND PROCESS FOR THEIR PREPARATION |
GB1368006A (en) * | 1972-08-24 | 1974-09-25 | Searle & Co | 4alpha,7alpha-carbonyl-5-cyano-17-hzydroxy-3-oxo-5beta,17alpha- pregnane-21-carboxylic acid ypsilon-lactone |
GB1455220A (en) * | 1973-09-14 | 1976-11-10 | Searle & Co | |
DE2627186A1 (en) * | 1976-03-05 | 1977-12-29 | Schering Ag | (17-Alpha)-(3)-hydroxypropyl-(17-beta)-hydroxy androstenones - aldosterone antagonist type diuretics and intermediates for spironolactone |
DE2609695A1 (en) * | 1976-03-05 | 1977-09-15 | Schering Ag | (17-Alpha)-(3)-hydroxypropyl-(17-beta)-hydroxy androstenones - aldosterone antagonist type diuretics and intermediates for spironolactone |
EP1223174A3 (en) * | 1996-12-11 | 2005-03-16 | G.D. Searle & Co. | Processes for preparation of 3-keto-7alpha-alkoxycarbonyl-delta-4,5- steroids and intermediates useful therein |
-
2005
- 2005-08-25 EP EP05805074A patent/EP1794177A2/en not_active Withdrawn
- 2005-08-25 JP JP2007530794A patent/JP2008512439A/en not_active Withdrawn
- 2005-08-25 WO PCT/IB2005/002757 patent/WO2006032970A2/en active Application Filing
- 2005-08-25 BR BRPI0515106-6A patent/BRPI0515106A/en not_active Application Discontinuation
- 2005-08-25 CA CA002579954A patent/CA2579954A1/en not_active Abandoned
- 2005-08-25 MX MX2007002846A patent/MX2007002846A/en unknown
- 2005-09-07 AR ARP050103739A patent/AR050632A1/en unknown
- 2005-09-08 TW TW094130861A patent/TW200617020A/en unknown
Also Published As
Publication number | Publication date |
---|---|
CA2579954A1 (en) | 2006-03-30 |
AR050632A1 (en) | 2006-11-08 |
WO2006032970A2 (en) | 2006-03-30 |
JP2008512439A (en) | 2008-04-24 |
TW200617020A (en) | 2006-06-01 |
EP1794177A2 (en) | 2007-06-13 |
MX2007002846A (en) | 2007-04-30 |
WO2006032970A3 (en) | 2006-08-17 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
B11A | Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing | ||
B11Y | Definitive dismissal - extension of time limit for request of examination expired [chapter 11.1.1 patent gazette] |