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1. (WO1998050572) HMG-CoA REDUCTASE INHIBITOR PREPARATION PROCESS
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/1998/050572 International Application No.: PCT/EP1998/002616
Publication Date: 12.11.1998 International Filing Date: 04.05.1998
Chapter 2 Demand Filed: 20.10.1998
IPC:
C07C 67/56 (2006.01) ,C07C 67/58 (2006.01) ,C07D 309/30 (2006.01) ,C12P 7/62 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
67
Preparation of carboxylic acid esters
48
Separation; Purification; Stabilisation; Use of additives
56
by solid-liquid treatment; by chemisorption
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
67
Preparation of carboxylic acid esters
48
Separation; Purification; Stabilisation; Use of additives
58
by liquid-liquid treatment
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
309
Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
16
having one double bond between ring members or between a ring member and a non-ring member
28
with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
30
Oxygen atoms, e.g. delta-lactones
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
P
FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
7
Preparation of oxygen-containing organic compounds
62
Carboxylic acid esters
Applicants:
DSM N.V. [NL/NL]; Het Overloon 1 NL-6411 TE Heerlen, NL (AllExceptUS)
SIBEIJN, Mieke [NL/NL]; NL (UsOnly)
BOUMAN, Andrianus, Johannes [NL/NL]; NL (UsOnly)
DE PATER, Robertus, Mattheus [NL/NL]; NL (UsOnly)
PURMER, Cornelis, Frederik [NL/NL]; NL (UsOnly)
Inventors:
SIBEIJN, Mieke; NL
BOUMAN, Andrianus, Johannes; NL
DE PATER, Robertus, Mattheus; NL
PURMER, Cornelis, Frederik; NL
Agent:
VISSER-LUIRINK, Gesina; Gist-Brocades B.V. Patents and Trademarks Dept. Wateringseweg 1 P.O. Box 1 NL-2600 MA Delft, NL
Priority Data:
97303111.507.05.1997EP
Title (EN) HMG-CoA REDUCTASE INHIBITOR PREPARATION PROCESS
(FR) PROCEDE DE PREPARATION D'INHIBITEURS DE REDUCTASE HMG-COA
Abstract:
(EN) A process for preparing a compound which is hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (such as lovastatin, compactin or pravastatin), or a precursor thereof, is disclosed where a broth containing the inhibitor (or its precursor) resulting from fermentation is basified prior to filtration to remove the biomass. The resulting filtrate is contacted with an adsorbent resin, acidified and the compound extracted using toluene, in which it is subsequently lactonized to give the inhibitor. The toluene containing the compound is then washed twice, firstly with alkaline, and then secondly with acidified water, before being isolated by crystallisation.
(FR) L'invention concerne un procédé pour préparer un composé qui est un inhibiteur de la réductase de la coenzyme A hydroxyméthyl glutaryl (HMG-CoA) (comme la lovastatine, la compactine ou la pravastatine) ou un précurseur de cette dernière. Selon ce procédé, un bouillon contenant l'inhibiteur (ou son précurseur) provenant de la fermentation est alcalinisé avant d'être filtré pour retirer la biomasse. Le filtrat ainsi obtenu est placé en contact avec une résine adsorbante, acidifiée et le composé extrait à l'aide de toluène, dans lequel il est ensuite lactonisé pour produire l'inhibiteur. Le toluène contenant le composé est ensuite lavé deux fois, une première fois avec de l'eau alcaline, puis une deuxième fois avec de l'eau acidifiée, avant d'être isolé par cristallisation.
Designated States: AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB, GE, GH, GM, GW, HU, ID, IL, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, US, UZ, VN, YU, ZW
African Regional Intellectual Property Organization (ARIPO) (GH, GM, KE, LS, MW, SD, SZ, UG, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
IL132786EP0980437US6268186JP2002510197 AU1998077613