WO2007034270A2 - Improved process for the preparation of (-) trans-n-methyl paroxetine - Google Patents
Improved process for the preparation of (-) trans-n-methyl paroxetine Download PDFInfo
- Publication number
- WO2007034270A2 WO2007034270A2 PCT/IB2006/002470 IB2006002470W WO2007034270A2 WO 2007034270 A2 WO2007034270 A2 WO 2007034270A2 IB 2006002470 W IB2006002470 W IB 2006002470W WO 2007034270 A2 WO2007034270 A2 WO 2007034270A2
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- WO
- WIPO (PCT)
- Prior art keywords
- methyl
- paroxetine
- trans
- formula
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims abstract description 21
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims abstract description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 13
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Chemical compound OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 claims abstract description 11
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims abstract description 10
- 229960002296 paroxetine Drugs 0.000 claims abstract description 9
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 claims abstract description 8
- UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 claims abstract description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 7
- -1 sulphonate compound Chemical class 0.000 claims abstract description 5
- MOJZPKOBKCXNKG-YJBOKZPZSA-N N-methylparoxetine Chemical compound C1([C@@H]2CCN(C[C@H]2COC=2C=C3OCOC3=CC=2)C)=CC=C(F)C=C1 MOJZPKOBKCXNKG-YJBOKZPZSA-N 0.000 claims description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- RYBSFHIQRSUBRI-UHFFFAOYSA-N 3-(chloromethyl)-4-(4-fluorophenyl)-1-methylpiperidine Chemical compound ClCC1CN(C)CCC1C1=CC=C(F)C=C1 RYBSFHIQRSUBRI-UHFFFAOYSA-N 0.000 description 2
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 2
- DENRAWQJOJWLNZ-UHFFFAOYSA-N 4-(4-fluorophenyl)-3-[(4-methoxyphenoxy)methyl]piperidine Chemical compound C1=CC(OC)=CC=C1OCC1C(C=2C=CC(F)=CC=2)CCNC1 DENRAWQJOJWLNZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- PTRITADCAOWGKC-UHFFFAOYSA-N (1-methyl-4-phenylpiperidin-3-yl)methanol Chemical compound OCC1CN(C)CCC1C1=CC=CC=C1 PTRITADCAOWGKC-UHFFFAOYSA-N 0.000 description 1
- WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- CXRHUYYZISIIMT-UHFFFAOYSA-N [4-(4-fluorophenyl)-1-methylpiperidin-3-yl]methanol Chemical compound OCC1CN(C)CCC1C1=CC=C(F)C=C1 CXRHUYYZISIIMT-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Definitions
- Paroxetine is an orally administered antidepressant for the treatment of depression, social anxiety disorders, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder and posttraumatic stress disorder.
- Paroxetine is marketed as Paxil® by GlaxoSmithKline.
- the '196 patent discloses obtaining N-methylparoxetine by reacting 4-(4- fluorophenyl)-3-chloromethyl-N-methyl-piperidine, also named CIPMA of structure (V):
- first N-methyl intermediate is prepared by reacting the sulfonate esters of the enantiomers of cis-4-(4-fluorophenyl)-3- hydroxymethyl-1-methylpiperidine with p-methoxyphenol.
- the '777 patent does not mention the yield in example 5.
- 38.5 grams of the ester were used to obtain 1.8 grams of the product as a free base, giving a yield of about 5%.
- N-methyl paroxetine by reacting the sulphonate ester with sesamol using toluene as a solvent.
- N-methylparoxetine produced results in lower yields of paroxetine.
- the low yield increases the cost of the process and requires additional purification.
- MIBK solvent methyl isobutyl ketone
- the main objective of the present invention is to provide an improved process for the preparation of compound of formula (I) using methyl isobutyl ketone (MIBK) as a solvent in presence of base potassium carbonate.
- MIBK methyl isobutyl ketone
- Another objective of the present invention is to provide a process for the preparation of compound of formula (I), which would be easy to implement on commercial scale and which can avoid the use of toxic solvents like toluene and benzene.
- Another objective of the present invention is to recover methyl isobutyl ketone
- MIBK methyl isobutyl ketone
- MIBK recovered methyl isobutyl ketone
- Still another objective of the present invention is to provide a process for the preparation of compound of formula (I) in good yield and high purity.
- the present invention provides an improved process for the preparation of (-) Trans-N-methyl paroxetine of formula (I), which involves the reaction of sulphonate ester of formula (III) with sesamol of formula (IV) in presence of base potassium carbonate using methyl isobutyl ketone (MIBK) as solvent at a temperature of about 118 -120° C.
- MIBK methyl isobutyl ketone
- the reaction step is performed in a solvent.
- the solvent is selected from the group consisting of methyl isobutyl ketone, methyl ethyl ketone, methyl vinyl ketone, methyl isopropyl ketone, methyl propyl ketone and N-methyl pyrrolidone; the most preferred solvent for this reaction is methyl isobutyl ketone (MIBK).
- the base used for the reaction is alkali carbonates selected from Sodium carbonate and Potassium carbonate preferably Potassium carbonate.
- the reacting step is preferably performed at a temperature of about 45° C to about 120° C. Most preferably; the reaction step is performed at a temperature of about 118° C to about 120° C.
- the starting material of this invention may be prepared according to the literature available in the prior art.
- the reaction mixture was refiuxed and simultaneously removed water azeotropically at 118-120 0 C for 5 hr in order to complete the reaction.
- the reaction mass was diluted with distilled water (100 ml) at 6O 0 C and stirred for 15 min at 60 0 C.
- the organic portion was separated and washed with distilled water (50ml).
- the organic portion was concentrated to a thick mass under vacuum at 60- 65°C.
- isopropyl alcohol (IPA) 50 ml
- the mass was concentrated under vacuum to remove solvents and to get residue.
- IPA 50ml
- 60 0 C To this residue, charged IPA (50ml) and heated to 60 0 C to get homogeneous solution.
- Distilled water (60ml) was charged under stirring at 60 0 C for 30 min.
- the slurry mass was cooled to 15 0 C and stirred for 60 min.
- the slurry was filtered at 15°C and washed the wet cake with 45 ml distilled water at 28-30 0 C.
- the wet cake was made reslurry-using n-hexane (15 ml) at 28-30°C and stirred for 60 min.
- the solid was filtered and washed with n-hexane (10 ml) at 28-30 0 C and dried the wet material to get 7.4 gm of N-methyl paroxetine (Purity > 97.5%).
Abstract
The present invention relates to an improved process for the preparation of (-) Trans-N-methyl paroxetine of formula (I), which is an intermediate in the synthesis of Paroxetine of formula (II). (-) Trans-N-methyl paroxetine is prepared by reacting (-) trans sulphonate compound of formula (III) with 3,4-methylenedioxyphenol ('sesamol') of formula (IV) in the presence of base potassium carbonate using Methyl isobutyl ketone (MIBK) as solvent.
Description
IMPROVED PROCESS FOR THE PREPARATION OF (-) TRANS-
N-METHYL PAROXETINE
Field of the Invention The present invention relates to an improved process for the preparation of
(-) Trans-N-methylparoxetine of formula (I) using methyl isobutyl ketone (MIBK) as solvent, which is a key intermediate in the synthesis of Paroxetine.
(I)
Background of the Invention
Paroxetine, trans (-)-3-[(l,3-benzodioxol-5-yloxy) methyl] -4-(4-fluorophenyl) piperidine, is a serotonin re-uptake inhibitor, and has the following structural formula (II):
CO
Paroxetine is an orally administered antidepressant for the treatment of depression, social anxiety disorders, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder and posttraumatic stress disorder. Paroxetine is marketed as Paxil® by GlaxoSmithKline.
U.S Patent 4,007,196 (henceforth ' 196) disclosed the process for the preparation of N-methylparoxetine using pyridine as solvent; the reaction scheme of the process is shown below:
The '196 patent discloses obtaining N-methylparoxetine by reacting 4-(4- fluorophenyl)-3-chloromethyl-N-methyl-piperidine, also named CIPMA of structure (V):
(V) with 3,4-methylenedioxyphenol ("sesamol") of structure (IV) to obtain N- raethylparoxetine.
(IV)
As per ' 196 patent CIPMA reacts with sesamol in a solution of sodium in methanol, giving N-methylparoxetine of the following structure (I) with a yield of about 25%.
(I)
U.S. Patent 4,585,777 (henceforth '777) is directed to the composition 4-(4- fluorophenyl)-3-((4-methoxyphenoxy)-methyl)-piperidine, which has the structure of:
(-) trans
In example 5 and 8 of '777 patent, first N-methyl intermediate is prepared by reacting the sulfonate esters of the enantiomers of cis-4-(4-fluorophenyl)-3- hydroxymethyl-1-methylpiperidine with p-methoxyphenol. The '777 patent does not mention the yield in example 5. In example 8, 38.5 grams of the ester were used to obtain 1.8 grams of the product as a free base, giving a yield of about 5%.
In U.S. Patent No. 3,912,743, example 1, a solution of 3-hydroxymethyl-l- methyl-4-phenyl piperidine in pyridine is reacted with methanesulphonyl chloride. The pyridine is removed and the crude resultant sulphonate ester is treated with sodium methoxide and 4-methoxyphenol in methanol under reflux. In Example 5 of EP 152 273, 4-(4-fluorophenyl)-3-hydroxymethyl-l -methyl piperidine is dissolved in toluene together with triethylamine and cooled. Benzenesulphonyl chloride is added to this mixture. The resultant solution of the benzenesulphonic ester is then mixed with sodium methoxide and 4-methoxyphenol in methyl isobutyl carbinol and heated.
US 2004/0087795 publication claims the process for the preparation of
N-methyl paroxetine by reacting the sulphonate ester with sesamol using toluene as a solvent.
Most of the prior art is directed to synthesis of CIPMA, related compounds and their precursors, rather than synthesis of N-methylparoxetine from CIPMA. For example, U.S. Patent No. 6,326,496, incorporated herein by reference, teaches obtaining CIPMA by reducing a precursor through the use of a metal hydride. These
patents provide little insight on how to synthesize N-methylparoxetine after obtaining CIPMA, or how to increase the yield of such synthesis.
The low yield of N-methylparoxetine produced results in lower yields of paroxetine. The low yield increases the cost of the process and requires additional purification.
None of the prior art references disclose or claim the use of solvent methyl isobutyl ketone (MIBK) for the preparation of compound of formula (I).
We focused our research to develop an improved and efficient process for the preparation of the compound of formula (I) in comparatively good yield and high purity. The process disclosed in the present invention is having advantages over the processes described in the above-mentioned prior art documents.
Objectives of the Invention
The main objective of the present invention is to provide an improved process for the preparation of compound of formula (I) using methyl isobutyl ketone (MIBK) as a solvent in presence of base potassium carbonate.
Another objective of the present invention is to provide a process for the preparation of compound of formula (I), which would be easy to implement on commercial scale and which can avoid the use of toxic solvents like toluene and benzene.
Another objective of the present invention is to recover methyl isobutyl ketone
(MIBK) and the recovered methyl isobutyl ketone (MIBK) is used in subsequent batches to make process more economical and commercially viable.
Still another objective of the present invention is to provide a process for the preparation of compound of formula (I) in good yield and high purity.
Summary of the Invention
Accordingly, the present invention provides an improved process for the preparation of (-) Trans-N-methyl paroxetine of formula (I), which involves the reaction of sulphonate ester of formula (III) with sesamol of formula (IV) in presence of base potassium carbonate using methyl isobutyl ketone (MIBK) as solvent at a temperature of about 118 -120° C.
(0
The process is shown in the scheme given below
Description of the Invention
In an embodiment of the present invention, the reaction step is performed in a solvent. The solvent is selected from the group consisting of methyl isobutyl ketone, methyl ethyl ketone, methyl vinyl ketone, methyl isopropyl ketone, methyl propyl ketone and N-methyl pyrrolidone; the most preferred solvent for this reaction is methyl isobutyl ketone (MIBK).
In still another embodiment of the present invention the base used for the reaction is alkali carbonates selected from Sodium carbonate and Potassium carbonate preferably Potassium carbonate.
In another embodiment of the present invention, the reacting step is preferably performed at a temperature of about 45° C to about 120° C. Most preferably; the reaction step is performed at a temperature of about 118° C to about 120° C.
The starting material of this invention may be prepared according to the literature available in the prior art.
The present invention is exemplified by the following example, which is provided for illustration only and should not be construed to limit the scope of the invention.
Example 1 Preparation of Compound of formula (I):
Preparation of (-) trans-4- (4'-fluorophenyl)-3-(3", 4"-methylenedioxyphenoxy methyl)- 1 -methyl piperidine [(-) Trans-N-methyl paroxetine].
10 gm (0.033 mol) of (3£4i?)-trans-4-(4-fluorophenyl)-l-methyl-3- methylsulphonyloxypiperidine and 30ml.of methyl isobutyl ketone (MIBK) were charged to a 500 ml 4-necked RB flask at 28-30°C.The contents were stirred to dissolve the mass completely. 4.6 gm (0.033 mol) of Sesamol was charged at 28-300C and stirred to dissolve. 6.7 gm (0.0483 mol) of dry potassium carbonate was charged to the mass under stirring at 28-300C. The reaction mixture was refiuxed and simultaneously removed water azeotropically at 118-1200C for 5 hr in order to complete the reaction. The reaction mass was diluted with distilled water (100 ml) at 6O0C and stirred for 15 min at 600C. The organic portion was separated and washed with distilled water (50ml). The organic portion was concentrated to a thick mass under vacuum at 60- 65°C. To the residue, isopropyl alcohol (IPA) (50 ml) was charged at 28-300C and heated to 60-650C. The mass was concentrated under vacuum to remove solvents and to get residue. To this residue, charged IPA (50ml) and heated to 600C to get homogeneous solution. Distilled water (60ml) was charged under stirring at 600C for 30 min. The slurry mass was cooled to 150C and stirred for 60 min. The slurry was filtered at 15°C and washed the wet cake with 45 ml distilled water at 28-300C. The
wet cake was made reslurry-using n-hexane (15 ml) at 28-30°C and stirred for 60 min. The solid was filtered and washed with n-hexane (10 ml) at 28-300C and dried the wet material to get 7.4 gm of N-methyl paroxetine (Purity > 97.5%).
Claims
Claim:
(I)A process for preparing (-) Trans-N-raethyl paroxetine of formula (I), which comprises: reacting the sulphonate ester of formula (III) with sesamol of formula (IV) in the presence of base potassium carbonate using methyl isobutyl ketone (MIBK) as solvent at reflux temperature.
(2) A process according to claim 1, wherein the wet cake of N-methyl paroxetine is further treated with hexane to get higher purity.
(3) A process according to claim 1, wherein (-) Trans-N-methyl paroxetine is used further for the preparation of Paroxetine.
(I) (III) (IV)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1346CH2005 | 2005-09-22 | ||
| IN1346/CHE/2005 | 2005-09-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2007034270A2 true WO2007034270A2 (en) | 2007-03-29 |
| WO2007034270A3 WO2007034270A3 (en) | 2007-11-15 |
Family
ID=37889170
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IB2006/002470 WO2007034270A2 (en) | 2005-09-22 | 2006-09-07 | Improved process for the preparation of (-) trans-n-methyl paroxetine |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2007034270A2 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030187269A1 (en) * | 1998-04-17 | 2003-10-02 | Curzons Alan David | Novel process |
-
2006
- 2006-09-07 WO PCT/IB2006/002470 patent/WO2007034270A2/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030187269A1 (en) * | 1998-04-17 | 2003-10-02 | Curzons Alan David | Novel process |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007034270A3 (en) | 2007-11-15 |
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