WO2001032642A1 - Method for the preparation of 5-carboxyphthalide - Google Patents

Method for the preparation of 5-carboxyphthalide Download PDF

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Publication number
WO2001032642A1
WO2001032642A1 PCT/DK2000/000585 DK0000585W WO0132642A1 WO 2001032642 A1 WO2001032642 A1 WO 2001032642A1 DK 0000585 W DK0000585 W DK 0000585W WO 0132642 A1 WO0132642 A1 WO 0132642A1
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WIPO (PCT)
Prior art keywords
carboxyphthalide
terephthalic acid
oleum
water
reaction
Prior art date
Application number
PCT/DK2000/000585
Other languages
French (fr)
Inventor
Hans Petersen
Poul Dahlberg Nielsen
Original Assignee
H. Lundbeck A/S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
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Application filed by H. Lundbeck A/S filed Critical H. Lundbeck A/S
Priority to BR0015471-7A priority Critical patent/BR0015471A/en
Priority to CA002389379A priority patent/CA2389379C/en
Priority to EP00969234A priority patent/EP1235819A1/en
Priority to AU79024/00A priority patent/AU7902400A/en
Priority to MXPA02004313A priority patent/MXPA02004313A/en
Priority to JP2001534793A priority patent/JP2003513084A/en
Publication of WO2001032642A1 publication Critical patent/WO2001032642A1/en
Priority to HR20020405A priority patent/HRP20020405A2/en
Priority to HK03104993A priority patent/HK1052702A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
    • C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3

Definitions

  • the present invention relates to a novel process for the preparation of 5-carboxyphthalide, a 5 starting material for the manufacture of the well-known antidepressant drug citalopram, l-[3- (dimethylamino)propyl]-l-(4-fluorophenyl)-l,3-dihydro-5-isobenzofurancarbonitrile.
  • Citalopram is a selective serotonin reuptake inhibitor which has successfully been marketed as an antidepressant drug for some years. It has the following structure:
  • 5-cyanophthalide is subjected to two successive Grignard reactions, i.e. with 4- fluorophenyl magnesium halogenide and N,N-dimethylaminopropyl magnesium halogenide, respectively, and the resulting dicarbinol compound is subjected to a ring closure reaction by dehydration.
  • the 5-cyanophthalide may in its turn be obtained by reaction of 5- carboxyphthalide with a dehydrating agent and a sulfonamide of the formula H 2 N-SO 2 -R
  • R is NH 2 , alkyloxy, optionally substituted phenyloxy, or substituted phenyl in order to obtain 5-cyanophthalide, cf. our co-pending Danish patent application No. PA199801718.
  • 5-Carboxyphthalide has been described as a useful intermediate in the polymer and paint industry. However, no reliable commercial source is available at present. A known process
  • trimellithic acid (DE-Al 2630927).
  • This process provides a mixture of the 5- and 6-carboxyphthalides and, accordingly, it requires elaborate and costly purification.
  • 5- carboxyphthalide is synthesised by reaction of terephthalic acid with trioxane in liquid SO 3 . During this process, trioxane sublimates and precipitates thereby obstructing the equipment.
  • 5-carboxyphthalide may be prepared from terephthalic acid in high yields by a convenient, cost-effective procedure. Description of the invention
  • the present invention provides a process for the manufacture of 5- carboxyphthalide
  • the oleum used is commercially available oleum. So the following are available from Aldrich/Fluka:
  • the terephthalic acid is condensed with paraformaldehyde liberating water, which reacts with the SO 3 .
  • 5-carboxyphthalide may be isolated as follows: The reaction mixture is hydrolysed with water. The condensed product, 5-carboxyphthalide inclusive possible diphthalide impurities may then be filtered off, and the 5-carboxyphthalide may be dissolved in aqueous medium by adjusting pH to about 6.7 to 7.3, leaving possible diphthalide impurities in the solid phase. The diphthalide present may be filtered off whereupon 5-carboxyphthalide may be precipitated by acidification, filtered off, washed with water and dried.
  • 1.0-1.33 equivalents CH 2 O and 1.0-2.5, preferably 1.0-2.0 are used. More preferably 1.25-1.5 equivalents SO, per equivalent terephthalic acid are used. Most preferably, about 1.37 equivalents (corresponding to about 3.3 kg 20-25% oleum/kg terephthalic acid) are used per equivalent terephthalic acid.
  • the reaction of terephthalic acid with paraformaldehyde is carried out at elevated temperature, conveniently at about 50-148 °C, preferably 115-125°C or 138-148°C.
  • the reaction time is not critical and may easily be determined by a person skilled in the art, a reaction time of 17-21 hours is preferably used for a 210 kg batch at 1 15-125°C. The time is decreased with increasing temperature.
  • the adjustment of pH to 6.3 to 7.3 in order to dissolve the 5-carboxyphthalide formed may be effected by NaOH, e.g. about 10% aqueous NaOH.
  • the terephthalic acid used as a starting material is commercially available.
  • the invention is further illustrated by the following example.
  • Example 1 5-Carboxyphthalid Terephthalic acid (10 kg) is charged into a reactor. Oleum (20% (18-24% SO 3 ); 6 kg/kg terephthalic acid ) is added and then paraformaldehyde (1.33 equivalents, 0.24 kg/kg terephthalic acid) is added. The mixture is agitated at 125 °C for 17 hours. Water (13 kg/kg terephthalic acid and filter aid is added, the temperature is adjusted to about 70 °C. The precipitate is filtered of, washed with water and suspended in water. The pH of the suspension is adjusted to about 7 with NaOH, activated carbon, 0.07 kg/kg terephthalic acid is added, and then the mixture is filtered, the precipitate is rinsed with water. The temperature of the filtrate is adjusted to about 65°C and the pH is adjusted to about 2 with 50% sulfuric acid. The 5-carboxyphthalide precipitated is separated by filtration washed and dried. Yield Example 2 5-Carboxyphthalid
  • Oleum (20-25% SO, 43 kg) is charged into a reactor.
  • Terephthalic acid (13 Kg ) and then paraformaldehyde (3.8 Kg) is added.
  • the mixture is agitated at 138-148 °C for 4'/ 2 hours.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Furan Compounds (AREA)
  • Indole Compounds (AREA)
  • Seasonings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

5-carboxyphthalide is obtained with very high purity and in high yields by a convenient process comprising reaction of terephthalic acid represented by formula (II), with paraformaldehyde HO(CH2)nH in oleum.

Description

METHOD FOR THE PREPARATION OF 5-CARBOXYPHTHALIDE
The present invention relates to a novel process for the preparation of 5-carboxyphthalide, a 5 starting material for the manufacture of the well-known antidepressant drug citalopram, l-[3- (dimethylamino)propyl]-l-(4-fluorophenyl)-l,3-dihydro-5-isobenzofurancarbonitrile.
Background of the Invention i o Citalopram is a selective serotonin reuptake inhibitor which has successfully been marketed as an antidepressant drug for some years. It has the following structure:
Figure imgf000002_0001
Formula I and it may be prepared by the process described in US Patent No 4,650,884 according to
15 which 5-cyanophthalide is subjected to two successive Grignard reactions, i.e. with 4- fluorophenyl magnesium halogenide and N,N-dimethylaminopropyl magnesium halogenide, respectively, and the resulting dicarbinol compound is subjected to a ring closure reaction by dehydration. The 5-cyanophthalide may in its turn be obtained by reaction of 5- carboxyphthalide with a dehydrating agent and a sulfonamide of the formula H2N-SO2-R
20 wherein R is NH2, alkyloxy, optionally substituted phenyloxy, or substituted phenyl in order to obtain 5-cyanophthalide, cf. our co-pending Danish patent application No. PA199801718.
5-Carboxyphthalide has been described as a useful intermediate in the polymer and paint industry. However, no reliable commercial source is available at present. A known process
25 comprises catalytic hydrogenation of trimellithic acid (DE-Al 2630927). This process provides a mixture of the 5- and 6-carboxyphthalides and, accordingly, it requires elaborate and costly purification. According to J. Org. Chem. 1970, 35, p. 1695-1696, 5- carboxyphthalide is synthesised by reaction of terephthalic acid with trioxane in liquid SO3. During this process, trioxane sublimates and precipitates thereby obstructing the equipment.
30
Though a number of other methods failed, it has now been found that 5-carboxyphthalide may be prepared from terephthalic acid in high yields by a convenient, cost-effective procedure. Description of the invention
Accordingly, the present invention provides a process for the manufacture of 5- carboxyphthalide
Figure imgf000003_0001
comprising reaction of terephthalic acid
Figure imgf000003_0002
with paraformaldehyde, HO(CH2)„H, in oleum.
By the process of the invention, 5-carboxyphthalide is obtained with very high purity and in high yields (> about 75%). Furthermore, as compared with the prior art process (J. Org. Chem. 1970, 35, p. 1695-1696), the process of the invention takes place without precipitation of sublimated trioxane which obstructs the equipment e.g. by precipitating in condensers.
The oleum used is commercially available oleum. So the following are available from Aldrich/Fluka:
12-17% SO3 (Fuming sulfuric acid) - 15% oleum 18-24% SO3 (Fuming sulfuric acid) = 20% oleum 27-33% SO3 (Fuming sulfuric acid) = 30% oleum From other sources 20% oleum contains 20-25% SO3
In the method of the invention, the terephthalic acid is condensed with paraformaldehyde liberating water, which reacts with the SO3. When the reaction is complete, 5-carboxyphthalide may be isolated as follows: The reaction mixture is hydrolysed with water. The condensed product, 5-carboxyphthalide inclusive possible diphthalide impurities may then be filtered off, and the 5-carboxyphthalide may be dissolved in aqueous medium by adjusting pH to about 6.7 to 7.3, leaving possible diphthalide impurities in the solid phase. The diphthalide present may be filtered off whereupon 5-carboxyphthalide may be precipitated by acidification, filtered off, washed with water and dried. Preferably 1.0-1.33 equivalents CH2O and 1.0-2.5, preferably 1.0-2.0 are used. More preferably 1.25-1.5 equivalents SO, per equivalent terephthalic acid are used. Most preferably, about 1.37 equivalents (corresponding to about 3.3 kg 20-25% oleum/kg terephthalic acid) are used per equivalent terephthalic acid.
The reaction of terephthalic acid with paraformaldehyde is carried out at elevated temperature, conveniently at about 50-148 °C, preferably 115-125°C or 138-148°C. The reaction time is not critical and may easily be determined by a person skilled in the art, a reaction time of 17-21 hours is preferably used for a 210 kg batch at 1 15-125°C. The time is decreased with increasing temperature.
The adjustment of pH to 6.3 to 7.3 in order to dissolve the 5-carboxyphthalide formed may be effected by NaOH, e.g. about 10% aqueous NaOH.
Acidification in order to precipitate the 5-carboxyphthalide may be carried out by adding sulphuric acid until pH = 2.
The terephthalic acid used as a starting material is commercially available.
Examples
The invention is further illustrated by the following example.
Example 1 5-Carboxyphthalid Terephthalic acid (10 kg) is charged into a reactor. Oleum (20% (18-24% SO3); 6 kg/kg terephthalic acid ) is added and then paraformaldehyde (1.33 equivalents, 0.24 kg/kg terephthalic acid) is added. The mixture is agitated at 125 °C for 17 hours. Water (13 kg/kg terephthalic acid and filter aid is added, the temperature is adjusted to about 70 °C. The precipitate is filtered of, washed with water and suspended in water. The pH of the suspension is adjusted to about 7 with NaOH, activated carbon, 0.07 kg/kg terephthalic acid is added, and then the mixture is filtered, the precipitate is rinsed with water. The temperature of the filtrate is adjusted to about 65°C and the pH is adjusted to about 2 with 50% sulfuric acid. The 5-carboxyphthalide precipitated is separated by filtration washed and dried. Yield Example 2 5-Carboxyphthalid
Oleum (20-25% SO, 43 kg) is charged into a reactor. Terephthalic acid (13 Kg ) and then paraformaldehyde (3.8 Kg) is added. The mixture is agitated at 138-148 °C for 4'/2 hours.
Water (87 L) is added and the temperature is adjusted to about 100 °C. The precipitate is filtered of, washed with water and suspended in water. The pH of the suspension is adjusted to about 7 with NaOH (about 10%), activated carbon, 0.5 Kg is added, and then the mixture is filtered, the precipitate is rinsed with water. The temperature of the filtrate is adjusted to about 85°C and the pH is adjusted to about 2 with 96% sulfuric acid. The 5-carboxyphthalide precipitated is separated by filtration washed and dried. Yield 82%.

Claims

1. A method for the preparation of 5-carboxyphthalide
Figure imgf000006_0001
comprising reaction of terephthalic acid
Figure imgf000006_0002
with paraformaldehyde HO(CH2)nH in oleum.
2. The method of any of Claim 1 wherein 1.0-1.33 equivalents CH2O and 1.0-2.5 equivalents SO3 per equivalent terephthalic acid are used
3. The method of Claim 2 wherein 1.0-2.0, in particular 1.25-1.5 equivalents SO3 per equivalent terephthalic acid are used.
4. The method of Claim 3 wherein about 1.37 equivalents SO3 per equivalent terephthalic acid are used.
5. The method of Claim 3 wherein about 3.3 kg 20-25% oleum is used per kg terephthalic acid.
PCT/DK2000/000585 1999-11-01 2000-10-19 Method for the preparation of 5-carboxyphthalide WO2001032642A1 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
BR0015471-7A BR0015471A (en) 1999-11-01 2000-10-19 Method for preparing 5-carboxyphthalide
CA002389379A CA2389379C (en) 1999-11-01 2000-10-19 Method for the preparation of 5-carboxyphthalide
EP00969234A EP1235819A1 (en) 1999-11-01 2000-10-19 Method for the preparation of 5-carboxyphthalide
AU79024/00A AU7902400A (en) 1999-11-01 2000-10-19 Method for the preparation of 5-carboxyphthalide
MXPA02004313A MXPA02004313A (en) 1999-11-01 2000-10-19 Method for the preparation of 5 carboxyphthalide.
JP2001534793A JP2003513084A (en) 1999-11-01 2000-10-19 Method for producing 5-carboxyphthalide
HR20020405A HRP20020405A2 (en) 1999-11-01 2002-05-10 Method for the preparation of 5-carboxyphthalide
HK03104993A HK1052702A1 (en) 1999-11-01 2003-07-10 Method for the preparation of 5-carboxyphthalide.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA199901569 1999-11-01
DKPA199901569 1999-11-01

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US (2) US6403813B1 (en)
EP (1) EP1235819A1 (en)
JP (1) JP2003513084A (en)
CN (1) CN1187348C (en)
AR (1) AR026063A1 (en)
AU (1) AU7902400A (en)
BR (1) BR0015471A (en)
CA (1) CA2389379C (en)
HK (1) HK1052702A1 (en)
HR (1) HRP20020405A2 (en)
IT (1) IT1319251B1 (en)
MX (1) MXPA02004313A (en)
WO (1) WO2001032642A1 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1118614A2 (en) † 2000-01-18 2001-07-25 Norpharma SpA Process for the preparation of 5-carboxyphthalide
WO2004083197A2 (en) * 2003-03-21 2004-09-30 H. Lundbeck A/S Intermediates for the preparation of citalopram and escitalopram
US6888009B2 (en) 1999-11-01 2005-05-03 H. Lundbeck A/S Method for the preparation of 5-carboxyphthalide
US7002025B2 (en) 2000-03-07 2006-02-21 Resolution Chemicals Limited Process for the preparation of citalopram
WO2006090409A1 (en) * 2005-02-28 2006-08-31 Kekule Pharma Ltd., An improved process for the preparation of 5 - carboxyphthalide
CN106632183A (en) * 2016-12-07 2017-05-10 万全万特制药（厦门）有限公司 Preparation method for oxalic acid Escitalopram impurity

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL198024B1 (en) 1999-04-14 2008-05-30 Lundbeck & Co As H Method for the preparation of citalopram
ITMI991581A1 (en) * 1999-06-25 2001-01-15 Lundbeck & Co As H METHOD FOR THE PREPARATION OF CITALOPRAM
PL355532A1 (en) 1999-12-28 2004-05-04 H.Lundbeck A/S Method for the preparation of citalopram
CZ20022627A3 (en) 1999-12-30 2002-10-16 H. Lundbeck A/S Process for preparing citalopram
SK286879B6 (en) * 2000-01-14 2009-07-06 H. Lundbeck A/S Method for the preparation of 5-cyanophthalide
NL1017417C1 (en) 2000-03-03 2001-03-16 Lundbeck & Co As H Process for the preparation of Citalopram.
JP2003527387A (en) 2000-03-13 2003-09-16 ハー・ルンドベック・アクチエゼルスカベット Method for producing citalopram
NL1017500C1 (en) 2000-03-13 2001-04-26 Lundbeck & Co As H Process for the preparation of Citalopram.
JP2003527385A (en) * 2000-03-13 2003-09-16 ハー・ルンドベック・アクチエゼルスカベット Stepwise alkylation of 5-substituted 1- (4-fluorophenyl) -1,3-dihydroisobenzofurans
PT1265882E (en) 2000-03-14 2004-06-30 Lundbeck & Co As H METHOD FOR PREPARING CITALOPRAM; COMPOUND AND CITALOPRAM
TR200202168T2 (en) * 2000-03-16 2002-12-23 H. Lundbeck A/S Preparation method of 5-Cyano-1- (4-Fluorophenyl) -1,3-Dihydroisobenzofurans
AR032455A1 (en) 2000-05-12 2003-11-12 Lundbeck & Co As H METHOD FOR THE PREPARATION OF CITALOPRAM, AN INTERMEDIARY EMPLOYED IN THE METHOD, A METHOD FOR THE PREPARATION OF THE INTERMEDIARY EMPLOYED IN THE METHOD AND PHARMACEUTICAL COMPOSITION ANTIDEPRESSIVE
US20050154052A1 (en) * 2003-03-24 2005-07-14 Hetero Drugs Limited Novel crystalline forms of (s)-citalopram oxalate
CN112062741A (en) * 2019-06-11 2020-12-11 太仓市茜泾化工有限公司 Preparation method of 5-carboxylic acid phthalide

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3607884A (en) * 1969-03-11 1971-09-21 Mobil Oil Corp Preparation of 5-carboxyphthalide in liquid sodium trioxide
DE2242007A1 (en) * 1972-08-26 1974-03-14 Basf Ag Phthalimidine and polyphthalimidine prepn - from diphthalides or mono-phthalide carboxylic acids and mono- or polyisocyanates reacted esp. in polar solvents
DE2630927A1 (en) * 1976-07-09 1978-01-19 Basf Ag METHOD FOR PRODUCING PHTHALIDOCARBONIC ACID- (5)

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1143703A (en) 1965-03-18
GB1526331A (en) 1976-01-14 1978-09-27 Kefalas As Phthalanes
GB8419963D0 (en) 1984-08-06 1984-09-12 Lundbeck & Co As H Intermediate compound and method
GB8814057D0 (en) 1988-06-14 1988-07-20 Lundbeck & Co As H New enantiomers & their isolation
DE59003859D1 (en) 1989-08-23 1994-01-27 Alusuisse Lonza Services Ag Sterilizable packaging container made of plastic-metal-plastic composite material and process for its production.
US5296507A (en) 1990-09-06 1994-03-22 H.Lundbeck A/S Treatment of cerbrovascular disorders
DE19626659A1 (en) * 1996-07-03 1998-01-08 Basf Ag Process for the production of phthalides
DE19627697A1 (en) * 1996-07-10 1998-01-15 Basf Ag Process for the production of phthalides
EA001728B1 (en) 1997-07-08 2001-08-27 Х.Лундбекк А/С Method for the praparation of citalopram
UA62985C2 (en) 1997-11-10 2004-01-15 Lunnbeck As H A method for the preparation of citalopram
SK283907B6 (en) 1997-11-11 2004-04-06 H. Lundbeck A/S A method for the preparation of citalopram
AU746665B2 (en) 1998-10-20 2002-05-02 H. Lundbeck A/S Method for the preparation of citalopram
BR9916955A (en) 1998-12-23 2001-09-11 Lundbeck & Co As H Method for preparing 5-cyanophthalide
AR022329A1 (en) 1999-01-29 2002-09-04 Lundbeck & Co As H METHOD FOR THE PREPARATION OF 5-CYANOFTALIDE
PL198024B1 (en) 1999-04-14 2008-05-30 Lundbeck & Co As H Method for the preparation of citalopram
ITMI991579A1 (en) 1999-06-25 2001-01-15 Lundbeck & Co As H METHOD FOR THE PREPARATION OF CITALOPRAM
ITMI991581A1 (en) 1999-06-25 2001-01-15 Lundbeck & Co As H METHOD FOR THE PREPARATION OF CITALOPRAM
CH692421A5 (en) 1999-10-25 2002-06-14 Lundbeck & Co As H Preparation of citalopram as antidepressant drug and for treating dementia and cerebrovascular disorders comprises reaction of a new intermediate with 3-(N,N-dimethylamino)propyl magnesium halide
WO2001032643A1 (en) 1999-11-01 2001-05-10 H. Lundbeck A/S Method for the preparation of 5-carboxyphthalide
US6310222B1 (en) 1999-11-01 2001-10-30 Sumika Fine Chemicals Co., Ltd. Production method of 5-phthalancarbonitrile compound, intermediate therefor and production method of the intermediate
AR026063A1 (en) 1999-11-01 2002-12-26 Lundbeck & Co As H METHOD FOR THE PREPARATION OF 5-CARBOXIFTALIDA.
IT1317729B1 (en) * 2000-01-18 2003-07-15 Norpharma S P A PROCEDURE FOR THE PREPARATION OF 5-CARBOXYPHTHALIDE.
US6433196B1 (en) * 2000-02-17 2002-08-13 Sumika Fine Chemicals Co., Ltd. Production method of citalopram, intermediate therefor and production method of the intermediate
IES20010143A2 (en) 2000-02-24 2001-07-25 Lundbeck & Co As H Method for the preparation of citalopram
NL1017415C1 (en) 2000-02-24 2001-05-18 Lundbeck & Co As H Process for the preparation of Citalopram.
GB0005477D0 (en) 2000-03-07 2000-04-26 Resolution Chemicals Limited Process for the preparation of citalopram
FI20011622A (en) 2000-08-18 2002-02-19 Lundbeck & Co As H Process for the preparation of citalopram
KR100430746B1 (en) 2000-12-28 2004-05-10 하. 룬트벡 아크티에 셀스카브 Process for the preparation of pure citalopram

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3607884A (en) * 1969-03-11 1971-09-21 Mobil Oil Corp Preparation of 5-carboxyphthalide in liquid sodium trioxide
DE2242007A1 (en) * 1972-08-26 1974-03-14 Basf Ag Phthalimidine and polyphthalimidine prepn - from diphthalides or mono-phthalide carboxylic acids and mono- or polyisocyanates reacted esp. in polar solvents
DE2630927A1 (en) * 1976-07-09 1978-01-19 Basf Ag METHOD FOR PRODUCING PHTHALIDOCARBONIC ACID- (5)

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LEROY S. FORNEY ET AL.: "The reaction of formaldehyde with deactivated benzoic acids. An ester-directed electrophilic aromatic substitution process", J. ORG. CHEM., vol. 36, no. 5, 1971, pages 689 - 693, XP002936414 *
LEROY S. FORNEY: "Reaction of terephthalic acid with formaldehyde in sulfur trioxide media", JOURNAL OF ORGANIC CHEMISTRY, vol. 35, no. 5, May 1970 (1970-05-01), pages 1695 - 1696, XP002936415 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6888009B2 (en) 1999-11-01 2005-05-03 H. Lundbeck A/S Method for the preparation of 5-carboxyphthalide
EP1118614A2 (en) † 2000-01-18 2001-07-25 Norpharma SpA Process for the preparation of 5-carboxyphthalide
EP1187822A1 (en) * 2000-01-18 2002-03-20 Norpharma SpA Process for the preparation of 5-carboxphthalide and its use for the production of citalopram
US6458973B1 (en) 2000-01-18 2002-10-01 Norpharma S.P.A. Process for the preparation of 5-carboxyphthalide
US6703516B2 (en) 2000-01-18 2004-03-09 Infosint Sa Process for the preparation of 5-carboxyphthalide
EP1118614B2 (en) † 2000-01-18 2011-03-09 Infosint Sa Process for the preparation of 5-carboxyphthalide
US7002025B2 (en) 2000-03-07 2006-02-21 Resolution Chemicals Limited Process for the preparation of citalopram
WO2004083197A2 (en) * 2003-03-21 2004-09-30 H. Lundbeck A/S Intermediates for the preparation of citalopram and escitalopram
WO2004083197A3 (en) * 2003-03-21 2004-10-28 Lundbeck & Co As H Intermediates for the preparation of citalopram and escitalopram
US7687645B2 (en) 2003-03-21 2010-03-30 H. Lundbeck A/S Intermediates for the preparation of citalopram and escitalopram
WO2006090409A1 (en) * 2005-02-28 2006-08-31 Kekule Pharma Ltd., An improved process for the preparation of 5 - carboxyphthalide
CN106632183A (en) * 2016-12-07 2017-05-10 万全万特制药（厦门）有限公司 Preparation method for oxalic acid Escitalopram impurity

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BR0015471A (en) 2002-07-09
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HRP20020405A2 (en) 2004-02-29
US6888009B2 (en) 2005-05-03
JP2003513084A (en) 2003-04-08
AR026063A1 (en) 2002-12-26
CN1391567A (en) 2003-01-15
US6403813B1 (en) 2002-06-11
CN1187348C (en) 2005-02-02
US20020165403A1 (en) 2002-11-07
MXPA02004313A (en) 2002-11-07
CA2389379A1 (en) 2001-05-10
IT1319251B1 (en) 2003-09-26
CA2389379C (en) 2007-04-10
ITMI20002342A1 (en) 2002-04-27
AU7902400A (en) 2001-05-14

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