78834-75-0

Basic information

• Product Name: Ethyl 7-chloro-2-oxoheptanoate
• Synonyms: ETHYL 7-CHLORO-2-OXOHEPTANOATE;Ethyl 7-Chloro-2-Otoheptanoate;7-Chloro-2-oxoheptanoic acid ethyl ester;Ethyl 7-chloro-2-oxohepanoate;ECO;ALPHA KETO ESTER (ETHYL 7-CHLORO-2-OXOHEPTANOATE);Heptanoic acid,7-chloro-2-oxo-, ethyl ester;ICK, active, GST tagged human
• CAS NO: 78834-75-0
• Molecular Formula: C₉H₁₅ClO₃
• Molecular Weight: 206.67
• EINECS: 278-992-1
• Product Categories: API
• Mol File: 78834-75-0.mol
• Article Data: 9

Chemical Properties

• Boiling Point: 281.2 °C at 760 mmHg
• Flash Point: 111.3 °C
• Appearance: /
• Density: 1.093 g/cm³
• Vapor Pressure: 0.00361mmHg at 25°C
• Refractive Index: 1.4510 to 1.4560
• Storage Temp.: -70°C
• Solubility: Acetonitrile (Slightly), Chloroform (Slightly), Ethyl Acetate (Slightly)
• CAS DataBase Reference: Ethyl 7-chloro-2-oxoheptanoate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 7-chloro-2-oxoheptanoate(78834-75-0)
• EPA Substance Registry System: Ethyl 7-chloro-2-oxoheptanoate(78834-75-0)

Safety Data

• Hazardous Substances Data: 78834-75-0(Hazardous Substances Data)

Usage

Chemical Properties

Colorless to Light orange to Yellow clear liquid.

Uses

Different sources of media describe the Uses of 78834-75-0 differently. You can refer to the following data:
1. Ethyl 7-Chloro-2-oxoheptanoate is a reagent used in the synthesis of selective BCL-XL inhibitor A1155463 used in the treatment of cancer.
2. Ethyl 7-chloro-2-oxoheptanoate is a product of the Grignard reaction that can be used to synthesize organic compounds. It has been used in the preparation of pharmaceuticals such as cilastatin, which is used to inhibit cytochrome P450 enzymes in order to prolong the effectiveness of other drugs. This reagent also reacts with hydrochloric acid to form ethyl chloride and heptanoic acid, which can be used for chlorination reactions.

Preparation

Ethyl 7-chloro-2-oxoheptanoate is an organochlorine compound that is obtained by reacting ethyl chloride with magnesium in the presence of benzene and cilastatin as a catalyst.

InChI:InChI=1/C9H15ClO3/c1-2-13-9(12)8(11)6-4-3-5-7-10/h2-7H2,1H3

Synthetic route

1-bromo-5-chloropentane (54512-75-3) + oxalic acid diethyl ester (95-92-1) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
Stage #1: 1-bromo-5-chloropentane; oxalic acid diethyl ester In tetrahydrofuran at -25 - -10℃; for 1h; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; water at 0℃; Reagent/catalyst; Inert atmosphere;	99.1%
Stage #1: 1-bromo-5-chloropentane With magnesium Stage #2: oxalic acid diethyl ester In tetrahydrofuran at -15℃; Stage #3: With hydrogenchloride In tetrahydrofuran Product distribution / selectivity;	90%
Grignard Reaction;

ethyl 7-chloro-α-hydroxyheptylate (1174680-07-9) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide In dichloromethane; water at -2 - 8℃; for 3h;	97%
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; potassium bromide In dichloromethane; water at -1 - 5℃; for 2.5h; Product distribution / selectivity;

C9H16ClO6S(1-)*Na(1+) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
With hydrogenchloride In water; toluene at 50 - 55℃; for 2h; Temperature; Solvent;	86.5%

ethanol (64-17-5) + C7H10ClNO → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
With sulfuric acid at 90℃; for 3.5h; Temperature;	78%

5-chloro-n-pentylmagnesium bromide (278605-08-6) + oxalic acid diethyl ester (95-92-1) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
Stage #1: 5-chloro-n-pentylmagnesium bromide; oxalic acid diethyl ester In tetrahydrofuran at -30 - 5℃; Stage #2: With hydrogenchloride In tetrahydrofuran Product distribution / selectivity;	74%

ethyl (E)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoate (1022895-93-7) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + (S)-2,2-dimethylcyclopropanecarboxamide (75885-58-4)

Conditions	Yield
Stage #1: ethyl (E)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoate With toluene-4-sulfonic acid In dichloromethane at 20℃; Stage #2: With sodium hydroxide; water In dichloromethane pH=8 - 9; Product distribution / selectivity;
Stage #1: ethyl (E)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoate With methanesulfonic acid In toluene at 30℃; Stage #2: With sodium hydroxide; water In toluene pH=8 - 9; Product distribution / selectivity;

6-chloro-1-hexanol (2009-83-8) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: sodium hydrogencarbonate; sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / potassium bromide / dichloromethane; water / 0.83 h / -5 - 10 °C 2.1: sodium hydrogensulfite / water / 2.67 h / 5 °C 2.2: 12 h / 5 - 20 °C 3.1: hydrogenchloride; water / 140 h / 25 °C 4.1: sulfuric acid / Reflux 5.1: sodium hydrogencarbonate; sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / potassium bromide / dichloromethane; water / 2.5 h / -1 - 5 °C View Scheme

6-chlorohexanal (52387-36-7) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydrogensulfite / water / 2.67 h / 5 °C 1.2: 12 h / 5 - 20 °C 2.1: hydrogenchloride; water / 140 h / 25 °C 3.1: sulfuric acid / Reflux 4.1: sodium hydrogencarbonate; sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / potassium bromide / dichloromethane; water / 2.5 h / -1 - 5 °C View Scheme
Multi-step reaction with 4 steps 1.1: water; sodium hydrogensulfite / 1 h / 35 °C 1.2: 0.5 h / 35 - 40 °C 2.1: water; potassium carbonate; dihydrogen peroxide / dimethyl sulfoxide / 5 h / 35 - 40 °C 3.1: sulfuric acid / 9 h / Reflux 4.1: sodium hydrogencarbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hypochlorite / water; dichloromethane / 3 h / -2 - 8 °C View Scheme

7-chloro-2-hydroxyheptanoic acid (1174680-06-8) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: sodium hydrogencarbonate; sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / potassium bromide / dichloromethane; water / 2.5 h / -1 - 5 °C View Scheme

7-chloro-α-hydroxyheptonitrile (1174680-05-7) → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride; water / 140 h / 25 °C 2: sulfuric acid / Reflux 3: sodium hydrogencarbonate; sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / potassium bromide / dichloromethane; water / 2.5 h / -1 - 5 °C View Scheme
Multi-step reaction with 3 steps 1: water; potassium carbonate; dihydrogen peroxide / dimethyl sulfoxide / 5 h / 35 - 40 °C 2: sulfuric acid / 9 h / Reflux 3: sodium hydrogencarbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hypochlorite / water; dichloromethane / 3 h / -2 - 8 °C View Scheme

7-chloro(1-oxoethyl)heptanoic acid ethyl ester → ethyl-7-Chloro-2-oxoheptanoate (78834-75-0)

Conditions	Yield
Stage #1: 7-chloro(1-oxoethyl)heptanoic acid ethyl ester With nitrosylsulfuric acid at 0 - 5℃; for 1h; Stage #2: With formaldehyd In 1,2-dichloro-ethane at 0 - 25℃; for 2h;

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + (S)-2,2-dimethylcyclopropanecarboxamide (75885-58-4) → (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester (877758-94-6)

Conditions	Yield
Stage #1: ethyl-7-Chloro-2-oxoheptanoate; (S)-2,2-dimethylcyclopropanecarboxamide With toluene-4-sulfonic acid In toluene for 10h; Reflux; Stage #2: at 30℃; for 1h; Solvent; Temperature; Irradiation;	99.5%

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + triphenylborane (960-71-4) → C15H21ClO2

Conditions	Yield
With phosphorous acid trimethyl ester In tetrahydrofuran at 50℃;	60%

aqueous formalin + ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + 1-bromo-5-chloropentane (54512-75-3) + sodium carbonate (497-19-8) → 7-chloro(1-oxoethyl)heptanoic acid ethyl ester

Conditions	Yield
With nitrosylsulfuric acid; sulfuric acid In water; toluene

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + (S)-2,2-dimethylcyclopropanecarboxamide (75885-58-4) → (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester (877758-94-6) + ethyl (E)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoate (1022895-93-7)

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + (S)-2,2-dimethylcyclopropanecarboxamide (75885-58-4) → ethyl 7-chloro-2-{[(1S)-2,2-dimethylcyclopropyl]formamido}hept-2-enoate (1022895-92-6)

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 20h; Heating / reflux;

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) + (S)-2,2-dimethylcyclopropanecarboxamide (75885-58-4) → (Z)-7-chloro-2 ((2s)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid (877674-77-6) + (E)-7-chloro-2[[(1S)-2,2-dimethyl cyclopropane]carboxamide]-2-heptenoic acid

Conditions	Yield
Stage #1: ethyl-7-Chloro-2-oxoheptanoate; (S)-2,2-dimethylcyclopropanecarboxamide; toluene-4-sulfonic acid In toluene for 20h; Reflux; Stage #2: With water; sodium hydroxide In toluene at 5 - 30℃; for 8h;

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → cilastatine (82009-34-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / toluene / 20 h / Reflux 1.2: 8 h / 5 - 30 °C 2.1: sodium hydroxide / methanol / 60 - 65 °C 2.2: pH 7 View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 20 h / Reflux 1.2: 8 h / 5 - 30 °C 2.1: hydrogenchloride / toluene; water / 4 h / 25 - 30 °C 3.1: sodium hydroxide / methanol / 60 - 65 °C 3.2: pH 7 View Scheme
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / toluene / 10 h / 130 °C 2: sodium hydroxide / cyclohexane; 1,4-dioxane / 12 h / 20 °C 3: 8.5 h / 55 - 60 °C / Inert atmosphere View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → (Z)-7-chloro-2 ((2s)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid (877674-77-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid / toluene / 20 h / Reflux 1.2: 8 h / 5 - 30 °C 2.1: hydrogenchloride / toluene; water / 4 h / 25 - 30 °C View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / toluene / 10 h / 130 °C 2: sodium hydroxide / cyclohexane; 1,4-dioxane / 12 h / 20 °C View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → cilastatin sodium

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 20 h / Reflux 1.2: 8 h / 5 - 30 °C 2.1: sodium hydroxide / methanol / 60 - 65 °C 2.2: pH 7 3.1: triethylamine / butan-1-ol / 25 - 30 °C 3.2: 3 h / 25 - 30 °C View Scheme
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid / toluene / 20 h / Reflux 1.2: 8 h / 5 - 30 °C 2.1: hydrogenchloride / toluene; water / 4 h / 25 - 30 °C 3.1: sodium hydroxide / methanol / 60 - 65 °C 3.2: pH 7 4.1: triethylamine / butan-1-ol / 25 - 30 °C 4.2: 3 h / 25 - 30 °C View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → α-Brom-δ-chlorvaleriansaeure-ethylester

Conditions	Yield
With bromine In tetrachloromethane at 20℃; for 1h;

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-chloropropyl)thiazole-4-carboxylate (1235034-74-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: bromine / tetrachloromethane / 1 h / 20 °C 2: ethanol / 6 h / 50 °C / Inert atmosphere View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-iodopropyl)thiazole-4-carboxylate (1235034-75-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine / tetrachloromethane / 1 h / 20 °C 2: ethanol / 6 h / 50 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 5 h / 90 °C / Inert atmosphere View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → C32H30N4O4S2

Conditions	Yield
Multi-step reaction with 4 steps 1.1: bromine / tetrachloromethane / 1 h / 20 °C 2.1: ethanol / 6 h / 50 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 5 h / 90 °C / Inert atmosphere 4.1: sodium hydride / N,N-dimethyl-formamide / 0.08 h / 20 °C 4.2: 1 h View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-phenoxypropyl)thiazole-4-carboxylic acid (1235032-77-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: bromine / tetrachloromethane / 1 h / 20 °C 2.1: ethanol / 6 h / 50 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 5 h / 90 °C / Inert atmosphere 4.1: sodium hydride / N,N-dimethyl-formamide / 0.08 h / 20 °C 4.2: 1 h 5.1: hydrogenchloride / water View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → 3-bromo-7-chloro-2-oxoheptanoate (1235035-22-9)

Conditions	Yield
With bromine In tetrachloromethane at 20℃; for 1h;

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(4-chlorobutyl)thiazole-4-carboxylate (1235035-23-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: bromine / tetrachloromethane / 1 h / 20 °C 2: N,N-dimethyl-formamide; ethanol / 6 h / 20 °C / Inert atmosphere View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → ethyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(4-iodobutyl)thiazole-4-carboxylate (1235035-24-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: bromine / tetrachloromethane / 1 h / 20 °C 2: N,N-dimethyl-formamide; ethanol / 6 h / 20 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 5 h / 90 °C / Inert atmosphere View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → C38H34N8O4S2

Conditions	Yield
Multi-step reaction with 4 steps 1.1: bromine / tetrachloromethane / 1 h / 20 °C 2.1: N,N-dimethyl-formamide; ethanol / 6 h / 20 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 5 h / 90 °C / Inert atmosphere 4.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C 4.2: 2 h / 20 °C View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → 5-(4-(4-(1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenoxy)butyl)-2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylic acid (1235033-32-5)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: bromine / tetrachloromethane / 1 h / 20 °C 2.1: N,N-dimethyl-formamide; ethanol / 6 h / 20 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 5 h / 90 °C / Inert atmosphere 4.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C 4.2: 2 h / 20 °C 5.1: sodium hydroxide / methanol; tetrahydrofuran; water / 5 h / 70 °C View Scheme

ethyl-7-Chloro-2-oxoheptanoate (78834-75-0) → Reaxys ID: 30580581

Upstream product

• 54512-75-3 1-bromo-5-chloropentane 
• 95-92-1 oxalic acid diethyl ester 
• 278605-08-6 5-chloro-n-pentylmagnesium bromide 
• 136879-36-2 7-chloro(1-oxoethyl)heptanoic acid ethyl ester 
• 64-17-5 ethanol 
• 1174680-05-7 7-chloro-α-hydroxyheptonitrile 
• 1174680-06-8 7-chloro-2-hydroxyheptanoic acid 
• 52387-36-7 6-chlorohexanal 
• 2009-83-8 6-chloro-1-hexanol 
• 1174680-07-9 ethyl 7-chloro-α-hydroxyheptylate 
• 1022895-93-7 ethyl (E)-7-chloro-2-((S)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoate 

Downstream Products

• 136879-36-2 7-chloro(1-oxoethyl)heptanoic acid ethyl ester 
• 877674-77-6 (Z)-7-chloro-2 ((2s)-2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid 
• 166037-21-4 (E)-7-chloro-2[[(1S)-2,2-dimethyl cyclopropane]carboxamide]-2-heptenoic acid 
• 82009-34-5 cilastatine 
• 166037-21-4 7-chloro-2-[[(1S)-2,2-dimethylcyclopropane]carboxamide]-2-heptenoic acid 

Relevant articles and documents

Intermediate for preparing n-7 -2 - halogenoisoheptanoic acid ethyl ester as well as synthesis method and application thereof

The invention relates to an intermediate for preparing 7-halogen-2-oxo ethyl oenanthate as well as a synthetic method and an application thereof. The application is preparation of 7-halogen-2-oxo ethyl oenanthate by the intermediate. 7-halogen-2-hydroyxl heptamide is prepared by means of a novel synthetic method. The 7-halogen-2-hydroyxl heptamide has good chemical stability and heat stability, and is easily purified, so that the process flow of preparing the 7-halogen-2-oxo ethyl oenanthate is simplified, the cost is lowered, the production environment is improved, and scaled production is facilitated.

Synthesis method of ethyl 7-chloro-2-oxohepanoate

The invention discloses a synthesis method of ethyl 7-chloro-2-oxohepanoate. According to the synthesis method, Mg, 1-bromo-5-chloropentane, tetrahydrofuran, hydrochloric acid, NaHCO3, chlorinated polystyrene resin, imidazole, acetonitrile and diethyl oxalate are used as main raw materials. The synthesis method is characterized by carrying out addition and hydrolysis reaction of diethyl oxalate and 1-bromo-5-chloropentane in the presence of an immobilized ionic catalyst PSIM-MgBr to obtain ethyl 7-chloro-2-oxohepanoate. Compared with the conventional synthesis method, the raw materials are used for directly preparing ethyl 7-chloro-2-oxohepanoate through activation reaction of the catalyst; the yield is greatly improved; the process flows and the production cost are reduced.

Purification method of ethyl 7-chloro-2-oxoheptanoate

The invention provides a purification method of ethyl 7-chloro-2-oxoheptanoate, wherein the purification method comprises the steps: firstly, carrying out a reaction of ethyl 7-chloro-2-oxoheptanoate oil crude product and a hydrosulphite solution, and separating to obtain a sulfite solid of ethyl 7-chloro-2-oxoheptanoate; then, dissolving the sulfite solid of ethyl 7-chloro-2-oxoheptanoate in water, adding an acid or alkali at a certain temperature, and decomposing the sulfite of ethyl 7-chloro-2-oxoheptanoate into ethyl 7-chloro-2-oxoheptanoate; and finally, extracting with an organic solvent immiscible with water, to obtain ethyl 7-chloro-2-oxoheptanoate having the purity improved. The method is simple in operation and suitable for industrialized production, and ensures the purity of a subsequent product and final product cilastatin sodium.