85118-25-8

Basic information

• Product Name: 1,3-dihydro-1-oxoisobenzofuran-5-carboxamide
• Synonyms: 1,3-dihydro-1-oxoisobenzofuran-5-carboxamide;1,3-Dihydro-1-oxo-5-isobenzofurancarboxamide;Einecs 285-678-8;1-oxo-1,3-dihydroisobenzofuran-5-carboxaMide;5-Carbamoylphthalide;EscitalopraM IMpurity L;Citalopram Impurity M
• CAS NO: 85118-25-8
• Molecular Formula: C₉H₇NO₃
• Molecular Weight: 177.15678
• EINECS: 285-678-8
• Mol File: 85118-25-8.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 420.8°Cat760mmHg
• Flash Point: 267°C
• Appearance: /
• Density: 1.419
• Vapor Pressure: 2.73E-07mmHg at 25°C
• Refractive Index: 1.631
• PKA: 15.40±0.20(Predicted)
• CAS DataBase Reference: 1,3-dihydro-1-oxoisobenzofuran-5-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 1,3-dihydro-1-oxoisobenzofuran-5-carboxamide(85118-25-8)
• EPA Substance Registry System: 1,3-dihydro-1-oxoisobenzofuran-5-carboxamide(85118-25-8)

Safety Data

• Hazardous Substances Data: 85118-25-8(Hazardous Substances Data)

Usage

Uses

5-Carbamoylphthalide is a key intermediate for citalopram synthesis.

InChI:InChI=1/C9H7NO3/c10-8(11)5-1-2-7-6(3-5)4-13-9(7)12/h1-3H,4H2,(H2,10,11)

Synthetic route

5-bromophthalide (64169-34-2) + carbon monoxide (201230-82-2) → 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8)

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); (2R)-1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(diphenylphosphino)ferrocene; ammonium carbamate; sodium hydrogencarbonate In 1,4-dioxane at 100℃; for 20h; Inert atmosphere;	72%

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8)

Conditions	Yield
With sulfuric acid
With sodium tetrahydroborate In ethanol; water at 80℃; for 1.5h;	92 %Chromat.

5-amino-3H-isobenzofuran-1-one (65399-05-5) → 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper (II)-sulfate; potassium cyanide / ueber eine wss. Diazoniumsalz-Loesung 2: aqueous sulfuric acid View Scheme

5-ethoxycarbonylphthalide (23405-31-4) → 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8)

Conditions	Yield
In methanol; ammonia

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) + chloro(chlorosulfanyl)methanone (2757-23-5) → 5-(1-oxo-1,3-dihydroisobenzofuran-5-yl)-1,3,4-oxathiazol-2-one (1313398-78-5)

Conditions	Yield
In 1,4-dioxane for 15h; Reflux;	80%
In 1,4-dioxane for 15h; Reflux;	80%

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 5-carboxyphtalide (4792-29-4)

Conditions	Yield
With sodium hydroxide anschliessend Ansaeuern;

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → (1-oxo-1,3-dihydroisobenzofuran-5-yl)carbonyl chloride (227954-90-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH solution / anschliessend Ansaeuern 2: thionyl chloride View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → methyl 1,3-dihydro-1-oxoisobenzofuran-5-carboxylate (23405-32-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. NaOH solution / anschliessend Ansaeuern 2: thionyl chloride 3: methanol View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 5-ethoxycarbonylphthalide (23405-31-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. NaOH solution / anschliessend Ansaeuern 2: thionyl chloride 3: ethanol View Scheme

thionyl chloride (7719-09-7) + 1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3)

Conditions	Yield
In N,N-dimethyl-formamide; toluene

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → ethyl 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carboxylate (1313398-80-9) + ethyl 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-5-carboxylate (1313398-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1,4-dioxane / 15 h / Reflux 2.1: 1,2-dichloro-benzene / 15 h / 150 °C 2.2: Resolution of mixture of two isomers View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carboxylic acid (1313398-82-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: 1,4-dioxane / 15 h / Reflux 2.1: 1,2-dichloro-benzene / 15 h / 150 °C 2.2: Resolution of mixture of two isomers 3.1: water; sodium hydroxide / ethanol / 4 h / 50 °C 3.3: 4 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → C15H9N3O3S

Conditions	Yield
Multi-step reaction with 5 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-5-carboxylic acid (1359020-80-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → C15H9N3O3S

Conditions	Yield
Multi-step reaction with 5 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → C14H13NO5S

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → C12H9NO5S

Conditions	Yield
Multi-step reaction with 3 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → ethyl 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carboxylate (1313398-80-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 5-(4-(hydroxymethyl)isothiazol-3-yl)isobenzofuran-1(3H)-one (1313398-84-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C 6: sodium tetrahydroborate / tetrahydrofuran; water / 0.08 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-4-carbaldehyde (1313398-86-5)

Conditions	Yield
Multi-step reaction with 7 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C 6: sodium tetrahydroborate / tetrahydrofuran; water / 0.08 h / 20 °C 7: pyridinium chlorochromate on silica gel / dichloromethane / 3 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → (E,Z)-5-((3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazol-4-yl)methylene)-2-thioxoimidazolidin-4-one (1313397-64-6)

Conditions

Yield

Multi-step reaction with 8 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C 6: sodium tetrahydroborate / tetrahydrofuran; water / 0.08 h / 20 °C 7: pyridinium chlorochromate on silica gel / dichloromethane / 3 h / 20 °C 8: acetic acid; 3-amino propanoic acid / 15 h / Reflux View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → ethyl 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-5-carboxylate (1313398-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 5-(5-(hydroxymethyl)isothiazol-3-yl)isobenzofuran-1(3H)-one (1313398-90-1)

Conditions	Yield
Multi-step reaction with 6 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C 6: sodium tetrahydroborate / tetrahydrofuran; water / 0.08 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → 3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazole-5-carbaldehyde (1313398-92-3)

Conditions	Yield
Multi-step reaction with 7 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C 6: sodium tetrahydroborate / tetrahydrofuran; water / 0.08 h / 20 °C 7: pyridinium chlorochromate on silica gel / dichloromethane / 3 h / 20 °C View Scheme

1-oxo-1,3-dihydroisobenzofuran-5-carboxamide (85118-25-8) → (E,Z)-5-((3-(1-oxo-1,3-dihydroisobenzofuran-5-yl)isothiazol-5-yl)methylene)-2-thioxoimidazolidin-4-one (1313397-65-7)

Conditions

Yield

Multi-step reaction with 8 steps 1: 1,4-dioxane / 15 h / Reflux 2: 1,2-dichloro-benzene / 15 h / 150 °C 3: sodium hydroxide / ethanol / 4 h / 50 °C 4: trifluoroacetic acid / dichloromethane / 4 h / 20 °C 5: tetrahydrofuran / 2 h / 20 °C 6: sodium tetrahydroborate / tetrahydrofuran; water / 0.08 h / 20 °C 7: pyridinium chlorochromate on silica gel / dichloromethane / 3 h / 20 °C 8: acetic acid; 3-amino propanoic acid / 15 h / Reflux View Scheme

Upstream product

• 82104-74-3 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile 
• 23405-31-4 5-ethoxycarbonylphthalide 
• 64169-34-2 5-bromophthalide 
• 201230-82-2 carbon monoxide 
• 65399-05-5 5-amino-3H-isobenzofuran-1-one 

Downstream Products

• 82104-74-3 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile 
• 23405-31-4 5-ethoxycarbonylphthalide 
• 23405-32-5 methyl 1-oxo-1,3-dihydro-5-isobenzofurancarboxylate 
• 227954-90-7 (1-oxo-1,3-dihydroisobenzofuran-5-yl)carbonyl chloride 
• 4792-29-4 5-carboxyphtalide 

Relevant articles and documents

Transition metal-free sodium borohydride promoted controlled hydration of nitriles to amides

A transition metal-free process, promoted by sodium borohydride, has been developed for convenient and selective hydration of nitriles to corresponding amides. The present process converts the aromatic, aliphatic, and heteroaromatic nitriles with wide functional group tolerance. The regioselective hydration of one nitrile moiety in the presence of an other nitrile group makes high impact in the present protocol.

Method for the preparation of 5-cyanophthalide

A method for the preparation of 5-cyanophthalide in which 5-carboxyphthalide is converted to the corresponding amide of Formula (IV) in which R is hydrogen or C1-6 alkyl, which is then reacted with a dehydrating agent thereby obtaining 5-cyanophthalide. The conversion of 5-carboxyphthalide to the corresponding amide of Formula (IV) may be carried out via the corresponding C1-6 alkyl or phenyl ester or the acid chloride, which is converted to the amide of Formula (IV) by amidation with ammonia or a C1-6 alkylamine. By the process 5-cyanophthalide, an important intermediate used in the preparation of the antidepressant citalopram, is prepared in high yields by a convenient, cost effective procedure.