150322-73-9

Basic information

• Product Name: Cyclopropyl 2-fluorobenzyl ketone
• Synonyms: Cyclopropyl 2-fluorobenzyl ketone;Ethanone, 1-cyclopropyl-2-(2-fluorophenyl)-;1-CYCLOPROPYL-2-(2-FLUORO-PHENYL)-ETHANONE;1-cyclopropyl-2-(2-fluorophenyl)-Ethanone (prasugrel);150322-73-91;1-Cyclopropyl-2-(2-fluorophenyl)ethan-1-one;Chemical intermediate for Prasugrel, Cyclopropyl 2-fluorobenzyl ketone;prasugrl I
• CAS NO: 150322-73-9
• Molecular Formula: C₁₁H₁₁FO
• Molecular Weight: 178.2
• EINECS: 1592732-453-0
• Product Categories: Drug Intermediates;Aromatics;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals;Erlotinib
• Mol File: 150322-73-9.mol
• Article Data: 17

Chemical Properties

• Boiling Point: 61°C/0.2mmHg(lit.)
• Flash Point: 107.942 °C
• Appearance: Pale Yellow Oil
• Density: 1.192 g/cm³
• Vapor Pressure: 0.018mmHg at 25°C
• Refractive Index: 1.5150-1.5190
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slig
• CAS DataBase Reference: Cyclopropyl 2-fluorobenzyl ketone(CAS DataBase Reference)
• NIST Chemistry Reference: Cyclopropyl 2-fluorobenzyl ketone(150322-73-9)
• EPA Substance Registry System: Cyclopropyl 2-fluorobenzyl ketone(150322-73-9)

Safety Data

• Hazardous Substances Data: 150322-73-9(Hazardous Substances Data)

Usage

Description

Cyclopropyl 2-fluorobenzyl ketone is a kind of ketone derivative. It is a kind of pharmacological intermediate. It is a pharmacological intermediate during the preparation of Prasugrel which is a kind of platelet inhibitors used for preventing the formation of blood clots.

References

Al Omari, Mahmoud MH, et al. "Chapter Four-Prasugrel Hydrochloride."Profiles of Drug Substances, Excipients and Related Methodology 40 (2015): 195-320.

Chemical Properties

Pale Yellow Oil

Uses

Different sources of media describe the Uses of 150322-73-9 differently. You can refer to the following data:
1. Atomoxetine intermediate
2. Prasugrel intermediate.
3. Prasugrel intermediate

InChI:InChI=1/C11H11FO/c12-10-4-2-1-3-9(10)7-11(13)8-5-6-8/h1-4,8H,5-7H2

Synthetic route

1-(2-fluorophenyl)but-3-en-2-one + dimethylsulfoxonium methylide (70775-39-2, 5367-24-8) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
In dichloromethane at 20℃; for 4h; Temperature;	93.6%

cyclopropanecarboxylic acid chloride (4023-34-1) + methyl o-fluorophenylacetate (57486-67-6) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
With pyridine In tetrahydrofuran at 20 - 60℃; for 6h; Solvent; Reagent/catalyst; Temperature;	92%

o-fluorophenylacetic acid ethyl ester (584-74-7) + cyclopropanecarboxylic acid chloride (4023-34-1) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
With pyridine In N,N-dimethyl-formamide at 20 - 30℃; for 8h; Solvent; Reagent/catalyst; Temperature;	91.4%

ethyl cyclopropylcarboxylate (4606-07-9) + (2-fluorophenyl)acetic acid (451-82-1) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
With sodium hydride In dimethyl sulfoxide; toluene at 95 - 110℃; for 1.5h; Large scale;	88%
Stage #1: (2-fluorophenyl)acetic acid With magnesium; isopropyl bromide In tetrahydrofuran; toluene at 15 - 65℃; Stage #2: ethyl cyclopropylcarboxylate In tetrahydrofuran; toluene at 5 - 65℃;

cyclopropanecarboxylic acid dimethylamide (17696-23-0) + 2-fluorobenzyl chloride (345-35-7) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: 2-fluorobenzyl chloride With iodine; magnesium In diethyl ether for 2h; Heating / reflux; Stage #2: cyclopropanecarboxylic acid dimethylamide In tetrahydrofuran; diethyl ether for 0.5h; Product distribution / selectivity;	79.8%
Stage #1: 2-fluorobenzyl chloride With iodine; magnesium In tert-butyl methyl ether for 2h; Heating / reflux; Stage #2: cyclopropanecarboxylic acid dimethylamide In tetrahydrofuran; tert-butyl methyl ether for 0.5h; Product distribution / selectivity;	60.9%
With iodine; magnesium In tetrahydrofuran; 2-methyltetrahydrofuran at 40 - 45℃; for 1.5h; Solvent; Concentration; Inert atmosphere;

2-(2-fluorophenyl)-N-methoxy-N-methylacetamide (946402-23-9) + cyclopropylmagnesium bromide (23719-80-4) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
In tetrahydrofuran at 45℃; for 1h; Inert atmosphere; Sealed tube;	78%
In tetrahydrofuran at 45℃; for 1h; Sealed tube; Inert atmosphere;	78%

o-fluorobenzyl bromide (446-48-0) + cyclopropropanecarbonitrile (5500-21-0) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: o-fluorobenzyl bromide With magnesium; methyl iodide In diethyl ether at 20℃; Stage #2: cyclopropropanecarbonitrile In diethyl ether at 20℃; Stage #3: With water; ammonium chloride In diethyl ether at 0℃; Product distribution / selectivity;	72.18%
Stage #1: o-fluorobenzyl bromide With magnesium In diethyl ether at 20℃; for 1h; Stage #2: cyclopropropanecarbonitrile In diethyl ether at 20℃; for 3.16667h; Heating / reflux; Stage #3: With water; ammonium chloride In diethyl ether; ethyl acetate Product distribution / selectivity; Saturated solution;
Stage #1: o-fluorobenzyl bromide With magnesium In diethyl ether at 25 - 30℃; for 0.5h; Stage #2: cyclopropropanecarbonitrile In diethyl ether at 25 - 30℃; for 4h; Heating / reflux; Stage #3: With water; ammonium chloride In diethyl ether Product distribution / selectivity;
Stage #1: o-fluorobenzyl bromide With iodine; magnesium In diethyl ether at 30℃; for 2.75h; Stage #2: cyclopropropanecarbonitrile In diethyl ether at 30℃; for 3h;

cyclopropanecarboxylic acid diethylamide (10374-28-4) + 2-fluorobenzyl chloride (345-35-7) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: 2-fluorobenzyl chloride With iodine; magnesium In diethyl ether for 2h; Heating / reflux; Stage #2: cyclopropanecarboxylic acid diethylamide In tetrahydrofuran; diethyl ether for 0.5h; Product distribution / selectivity;	48.7%

cyclopropanecarboxylic acid diisopropylamide (61259-30-1) + 2-fluorobenzyl chloride (345-35-7) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: 2-fluorobenzyl chloride With iodine; magnesium In diethyl ether for 2h; Heating / reflux; Stage #2: cyclopropanecarboxylic acid diisopropylamide In tetrahydrofuran; diethyl ether for 2h; Product distribution / selectivity;	22.5%

o-fluorobenzyl bromide (446-48-0) + magnesium dihydride (7439-95-4) + cyclopropropanecarbonitrile (5500-21-0) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
In diethyl ether

cyclopropropanecarbonitrile (5500-21-0) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: o-fluorobenzyl bromide With magnesium In diethyl ether at 20℃; for 1h; Stage #2: cyclopropropanecarbonitrile In diethyl ether at 20℃; for 3.16667h; Heating / reflux;

cyclopropanecarboxylic acid chloride (4023-34-1) + 2-fluorobenzyl chloride (345-35-7) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) + 2-Fluorotoluene (95-52-3) + 2-fluorobenzyl alcohol (446-51-5) + cyclopropanecarboxylic acid (1759-53-1)

Conditions	Yield
Stage #1: 2-fluorobenzyl chloride With iodine; magnesium In diethyl ether for 2h; Heating / reflux; Stage #2: cyclopropanecarboxylic acid chloride In tetrahydrofuran; diethyl ether at -70 - 20℃; Stage #3: With water; ammonium chloride Product distribution / selectivity;

2-fluorobenzyl chloride (345-35-7) + cyclopropropanecarbonitrile (5500-21-0) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) + 2-Fluorotoluene (95-52-3) + 2-fluorobenzyl alcohol (446-51-5)

Conditions	Yield
Stage #1: 2-fluorobenzyl chloride With iodine; magnesium In diethyl ether for 2h; Heating / reflux; Stage #2: cyclopropropanecarbonitrile In tetrahydrofuran; diethyl ether at -50℃; for 0.5h; Heating / reflux; Stage #3: With hydrogenchloride; water Product distribution / selectivity;

(2-fluorophenyl)acetic acid (451-82-1) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 0.25 h / 0 - 5 °C 1.2: 6 h / 0 - 5 °C 2.1: iodine; magnesium / tetrahydrofuran / 25 - 50 °C 2.2: 40 - 50 °C 2.3: 0.25 h / 0 - 30 °C View Scheme

2-(2-fluorophenyl)-N-methoxy-N-methylacetamide (946402-23-9) + cyclopropyl bromide (4333-56-6) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: cyclopropyl bromide With iodine; magnesium In tetrahydrofuran at 25 - 50℃; Stage #2: 2-(2-fluorophenyl)-N-methoxy-N-methylacetamide In tetrahydrofuran at 40 - 50℃; Stage #3: With hydrogenchloride In tetrahydrofuran; water at 0 - 30℃; for 0.25h;
Stage #1: 2-(2-fluorophenyl)-N-methoxy-N-methylacetamide; cyclopropyl bromide With iodine; magnesium In tetrahydrofuran at 40 - 50℃; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 0 - 30℃; for 0.25h;

methyl cyclopropylcarboxylate (2868-37-3) + (2-fluorophenyl)acetic acid (451-82-1) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Stage #1: (2-fluorophenyl)acetic acid With magnesium; isopropyl bromide In tetrahydrofuran; toluene at 15 - 65℃; Stage #2: methyl cyclopropylcarboxylate In tetrahydrofuran; toluene at 5 - 65℃;

2-fluorobenzyl chloride (345-35-7) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetrabutylammomium bromide / dichloromethane; water / 25 °C 2.1: sodium hydroxide; water / 5 - 95 °C 2.2: pH 2 - 3 3.1: magnesium; isopropyl bromide / toluene; tetrahydrofuran / 15 - 65 °C 3.2: 5 - 65 °C View Scheme
Multi-step reaction with 3 steps 1.1: tetrabutylammomium bromide / dichloromethane; water / 25 °C 2.1: sodium hydroxide; water / 5 - 95 °C 2.2: pH 2 - 3 3.1: magnesium; isopropyl bromide / toluene; tetrahydrofuran / 15 - 65 °C 3.2: 5 - 65 °C View Scheme

2-fluorophenyl acetonitrile (326-62-5) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide; water / 5 - 95 °C 1.2: pH 2 - 3 2.1: magnesium; isopropyl bromide / toluene; tetrahydrofuran / 15 - 65 °C 2.2: 5 - 65 °C View Scheme
Multi-step reaction with 2 steps 1.1: sodium hydroxide; water / 5 - 95 °C 1.2: pH 2 - 3 2.1: magnesium; isopropyl bromide / toluene; tetrahydrofuran / 15 - 65 °C 2.2: 5 - 65 °C View Scheme

2-(2-fluorophenyl acetic acid) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / dicyclohexyl-carbodiimide; benzotriazol-1-ol / dichloromethane / 6 h / 0 - 5 °C 2.1: iodine; magnesium / tetrahydrofuran / 40 - 50 °C 2.2: 0.25 h / 0 - 30 °C View Scheme

cyclopropanecarboxylic acid dimethylamide (17696-23-0) + 2-fluorobenzyl chloride (345-35-7) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) + 1,2-bis(2-fluorophenyl)ethane (349-38-2)

Conditions	Yield
With iodine; magnesium In tetrahydrofuran; toluene at 40 - 45℃; for 1.5h; Inert atmosphere;	A n/a B 7.6 %Chromat.

2-(2-fluorophenyl)-5,5-dimethyl-[1,3,2]dioxaborinane (346656-39-1) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; copper(II) bis(trifluoromethanesulfonate) / N,N-dimethyl acetamide / 80 h / 20 °C / Sealed tube 2: tetrahydrofuran / 1 h / 45 °C / Inert atmosphere; Sealed tube View Scheme

fluorobenzene (462-06-6) → 1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: tin(IV) chloride / tetrahydrofuran / 4 h / 45 °C 2: dichloromethane / 4 h / 20 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)ethanone (204205-33-4)

Conditions	Yield
With iodine(I) bromide; 1-n-butyl-3-methylimidazolim bromide In tetrahydrofuran at 40℃; for 4h; Temperature; Time; Concentration;	95.3%
With bromine In methanol at 25 - 30℃; for 6h; Concentration;	94.65%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; 2,2'-azobis(isobutyronitrile) In cyclohexane at 10℃; Product distribution / selectivity; Reflux;	93.28%

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → [2H]-cyclopropyl 2-fluorobenzyl ketone (1646868-75-8)

Conditions	Yield
With pyrrolidine; water-d2 In 1,4-dioxane at 20℃; for 12h;	90%

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → α-cyclopropylcarbonyl-2-fluorobenzyl chloride (178688-43-2)

Conditions	Yield
With hydrogenchloride; dihydrogen peroxide In 1,4-dioxane; water at 20 - 80℃; for 2 - 72h; Product distribution / selectivity;	82.9%
With chlorine In dichloromethane at 5 - 20℃; for 5.5h; Product distribution / selectivity;	81%
With chlorine In dichloromethane at 0℃; for 5.3h;	80%

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) + 4-methoxy-aniline (104-94-9) → cyclopropanecarboxylic acid (4-methoxy-phenyl)-amide (2759-47-9)

Conditions	Yield
With 2,2,6,6-tetramethyl-piperidine; trifluorormethanesulfonic acid; oxygen In m-xylene at 130℃; under 760.051 Torr; for 6h; Sealed tube;	60%

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 5-chloro-1-(2-fluorophenyl)-pentan-2-one (1056459-35-8)

Conditions	Yield
With hydrogenchloride; water at 100℃; for 2.5h;
With hydrogenchloride In water for 3h;

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → prasugel (150322-43-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -60 - 0 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 3.33 h / 10 - 30 °C View Scheme
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 6 h / 25 - 30 °C 2.3: 6.5 h / 0 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 3.33 h / 10 - 30 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one (150322-38-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -60 - 0 °C View Scheme
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C View Scheme
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C View Scheme
Multi-step reaction with 2 steps 1: 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / toluene-4-sulfonic acid / dichloromethane / 4.75 h / 0 - 5 °C / Reflux 2: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → CS-747 hydrochloride

Conditions	Yield
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -60 - 0 °C 4.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 3.33 h / 10 - 30 °C 5.1: hydrogenchloride / ethyl acetate; acetone / 0.75 h / 25 - 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 6 h / 25 - 30 °C 2.3: 6.5 h / 0 - 30 °C 3.1: hydrogenchloride / ethyl acetate; acetone / 0.75 h / 25 - 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C 3.1: N-ethyl-N,N-diisopropylamine / acetonitrile / 3.33 h / 10 - 30 °C 4.1: hydrogenchloride / ethyl acetate; acetone / 0.75 h / 25 - 55 °C / Inert atmosphere View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine hydrobromide (1243654-57-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -60 - 0 °C 4.1: hydrogen bromide / water; acetone / 1 h / 0 - 5 °C View Scheme
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C 2.3: 8 h / 0 - 25 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C 3.1: hydrogen bromide / water; acetone / 1 h / 0 - 5 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydro thieno[3,2-c] pyridine hydrochloride (150322-39-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3.1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -60 - 0 °C 4.1: hydrogen bromide / water; acetone / 1 h / 0 - 5 °C 5.1: ammonia / dichloromethane; water / 0 - 30 °C 5.2: 1 h / 25 - 30 °C View Scheme
Multi-step reaction with 2 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C 2.3: 1 h / 25 - 30 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2.1: potassium carbonate / acetonitrile / 0.5 h / 25 - 30 °C 2.2: 7 h / 25 - 30 °C 2.3: 8 h / 0 - 25 °C 3.1: ammonia / dichloromethane; water / 0 - 30 °C 3.2: 1 h / 25 - 30 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 1-cyclopropyl-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)ethanone hydrobromide salt (1287752-37-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid; 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / chloroform / 4 h / Reflux 2: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3: hydrogen bromide / water; acetone / 5 h / 0 - 30 °C View Scheme
Multi-step reaction with 3 steps 1: 2,2'-azobis(isobutyronitrile); N-Bromosuccinimide / toluene-4-sulfonic acid / dichloromethane / 4.75 h / 0 - 5 °C / Reflux 2: potassium carbonate / acetonitrile / 5 h / 25 - 35 °C 3: hydrogen bromide / water; acetone / 5.25 h / 0 - 30 °C View Scheme

1-cyclopropyl-2-(2-fluorophenyl)ethanone (150322-73-9) → 2-(tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (952340-38-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: dibenzoyl peroxide; N-Bromosuccinimide / ethyl acetate / 25 - 60 °C 2: triethylamine / dichloromethane / 20 °C / Inert atmosphere View Scheme

Upstream product

• 4606-07-9 ethyl cyclopropylcarboxylate 
• 451-82-1 (2-fluorophenyl)acetic acid 
• 4023-34-1 cyclopropanecarboxylic acid chloride 
• 57486-67-6 methyl o-fluorophenylacetate 
• 584-74-7 o-fluorophenylacetic acid ethyl ester 
• 70775-39-2 dimethylsulfoxonium methylide 
• 462-06-6 fluorobenzene 
• 346656-39-1 2-(2-fluorophenyl)-5,5-dimethyl-[1,3,2]dioxaborinane 
• 946402-23-9 2-(2-fluorophenyl)-N-methoxy-N-methylacetamide 
• 23719-80-4 cyclopropylmagnesium bromide 
• 17696-23-0 cyclopropanecarboxylic acid dimethylamide 
• 345-35-7 2-fluorobenzyl chloride 
• 326-62-5 2-fluorophenyl acetonitrile 
• 2868-37-3 methyl cyclopropylcarboxylate 

Downstream Products

• 204205-33-4 2-bromo-1-cyclopropyl-2-(2-fluorophenyl)ethanone 
• 150322-43-3 prasugel 
• 150322-38-6 5-(2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl)-5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one 
• 1243654-57-0 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydrothieno[3,2-c]pyridine hydrobromide 
• 150322-39-7 5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-2-oxo-2,4,5,6,7,7a-hexahydro thieno[3,2-c] pyridine hydrochloride 
• 1287752-37-7 1-cyclopropyl-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)ethanone hydrobromide salt 
• 952340-38-4 2-(tert-butyldimethylsilyloxy)-5-(α-cyclopropylformyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 1056459-37-0 2-acetoxy-5-[5-chloro-1-(2-fluorophenyl)-2-oxopentyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 1373350-56-1 5-bromo-1-(2-fluorophenyl)-pentan-2-one 
• 1373350-58-3 1-bromo-5-chloro-1-(2-fluorophenyl)-pentan-2-one 
• 1373350-57-2 1,5-Dibromo-1-(2-fluorophenyl)-pentan-2-one 
• 1373350-61-8 2-acetoxy-5-[5-chIoro-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine maleate 
• 1373350-59-4 2-acetoxy-5-[5-bromo-1-(2-fluorophenyl)pentyl]-4,5,6,7-tetrahydro-4H-thieno[3,2-c] pyridine 
• 2759-47-9 cyclopropanecarboxylic acid (4-methoxy-phenyl)-amide 

Relevant articles and documents

2 - Bromo 2 - (2 - fluorophenyl) ethanone preparation of cyclopropyl (by machine translation)

The invention belongs to the technical field of medicines and particularly relates to a preparation method of a medicine intermediate, and more particularly relates to a preparation method of a prasugrel intermediate cyclopropyl-2-bromo-2-(2-fluorophenyl) ethanone. The preparation method comprises the following steps: carrying out reaction on 2-fluorophenylacetate and cyclopropane carbonyl chloride to prepare cyclopropyl-2-(2-fluorophenyl) ethanone; and then, carrying out halogenating reaction with a bromination reagent to prepare cyclopropyl-2-bromo-2-(2-fluorophenyl) ethanone. The preparation method provided by the invention is carried out under a relatively mild condition, raw materials are easily available, and the obtained product is high in purity and relatively high in yield which reaches over 70%, so that the preparation method is suitable for industrial production.

PROCESS FOR THE PREPARATION OF HIGH-PURITY PRASUGREL

The field of invention relates to a novel process, suitable for industrial scale manufacture, for the preparation of high-purity 5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7- tetrahydrothieno[3,2-c]pyridine-2-yl acetate, prasugrel, of Formula (I). Especially in large-scale production, one of the main causes of piling up the impurities is the use of ether solvents consequently in each step in this procedure ethers are excluded. Avoiding the ethers resulted new conditions for production of intermediates in the different steps of our procedure. Conditions were determined so that each step from the beginning contributes to minimizing the impurity content of the end-product.

Ambient Decarboxylative Arylation of Malonate Half-Esters via Oxidative Catalysis

We report decarboxylative carbonyl α-arylation by coupling of arylboron nucleophiles with malonic acid derivatives. This process is enabled by the merger of aerobic oxidative Cu catalysis with decarboxylative enolate interception reminiscent of malonyl-CoA reactivity in polyketide biosynthesis. This method enables the synthesis of monoaryl acetate derivatives containing electrophilic functional groups that are incompatible with existing α-arylation reactivity paradigms. The utility of the reaction is demonstrated in drug intermediate synthesis and late-stage functionalization.