162096-54-0

Basic information

• Product Name: 4-(CYCLOPROPYL CARBONYL)-A,A-DIMETHYLPHENYL ACETIC ACID
• Synonyms: 4-(CYCLOPROPYL CARBONYL)-A,A-DIMETHYLPHENYL ACETIC ACID;4-(Cyclopropylcarbonyl)-alpha,alpha-dimethylphenyl acetic acid;4-(Cyclopropylcarbonyl)-alpha,alpha-dimethylbenzeneacetic acid;4-(Cyclopropylcarbonyl)-α,α-dimethylbenzeneacetic Acid;2-(4-(cyclopropanecarbonyl)phenyl)-2-methylpropanoic acid;Benzeneacetic acid,4-(cyclopropylcarbonyl)-a,a-diMethyl-;2-(4-(cyclopropanecarbonyl)phenyl);Alpha, alpa-4-[1-oxo-1-1-Cycloporpyl]phenyl Acetic Acid
• CAS NO: 162096-54-0
• Molecular Formula: C₁₄H₁₆O₃
• Molecular Weight: 232.27504
• Product Categories: Aromatics;Intermediates
• Mol File: 162096-54-0.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 399.255 °C at 760 mmHg
• Flash Point: 209.424 °C
• Appearance: /
• Density: 1.213 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.576
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly)
• PKA: 4.17±0.10(Predicted)
• CAS DataBase Reference: 4-(CYCLOPROPYL CARBONYL)-A,A-DIMETHYLPHENYL ACETIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(CYCLOPROPYL CARBONYL)-A,A-DIMETHYLPHENYL ACETIC ACID(162096-54-0)
• EPA Substance Registry System: 4-(CYCLOPROPYL CARBONYL)-A,A-DIMETHYLPHENYL ACETIC ACID(162096-54-0)

Safety Data

• Hazardous Substances Data: 162096-54-0(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 162096-54-0 differently. You can refer to the following data:
1. 4-(Cyclopropylcarbonyl)-α,α-dimethylbenzeneacetic Acid is used for preparation of Terfenadine ((T114500) analogs.
2. 4-(Cyclopropylcarbonyl)-α,α-dimethylbenzeneacetic Acid is used for the preparation of Terfenadine ((T114500) analogs.

InChI:InChI=1/C14H16O3/c1-14(2,13(16)17)11-7-5-10(6-8-11)12(15)9-3-4-9/h5-9H,3-4H2,1-2H3,(H,16,17)

Synthetic route

2-(4-(1-Oxo-1-cyclopropanyl)-phenyl)-2-methyl propanyl acetate (169280-24-4) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
With nitric acid; sodium nitrite In acetic acid at 48 - 50℃; for 2h;	90%
With nitric acid; sodium nitrite In water; acetic acid at 48 - 50℃; for 5.5h; Heating / reflux;	90%

2-(4-(1-Oxo-1-cyclopropanyl)-phenyl)-2-methylpropanol (169280-26-6) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
With ruthenium trichloride; sodium periodate In tetrachloromethane; water; acetonitrile at 20℃; for 1h;	90%
With sodium periodate; ruthenium trichloride In tetrachloromethane; acetonitrile at 20℃; for 1h;	90%
With nitric acid; sodium nitrite In acetic acid at 48 - 50℃; for 2h;	83%

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionitrile (169280-06-2) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
With sodium hydroxide In ethanol for 21h; Heating / reflux;	70%
With hydrogenchloride In sodium hydroxide; ethanol; dichloromethane	70%
With hydrogenchloride In sodium hydroxide; ethanol; dichloromethane	70%
With sodium hydroxide In ethanol for 21h; Heating / reflux;	70%

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionamide (169280-22-2) + ethanol (64-17-5) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
With hydrogenchloride for 10h; Heating / reflux;

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionamide (169280-22-2) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
In ethanol

benzene (71-43-2) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sulfuric acid / 20 °C 2.1: 1-methyl-pyrrolidin-2-one / 160 - 165 °C 3.1: aluminum (III) chloride / dichloromethane / 0 - 5 °C / Inert atmosphere 3.2: 0 °C / Inert atmosphere 4.1: sodium hydroxide; methanol / 2 h / 20 °C 5.1: potassium permanganate; acetic acid / water; acetone / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: aluminum (III) chloride; propylene glycol / acetic acid methyl ester / 0 - 5 °C 2.1: aluminum (III) chloride / dichloromethane / 2.33 h / -5 - 0 °C 2.2: 5 h / 0 °C 3.1: methanol; sodium hydroxide / 4 h / 25 - 30 °C 4.1: water; acetic acid; potassium permanganate / acetone / 7 h / 25 - 45 °C View Scheme

(2-acetoxy-1,1-dimethylethyl)benzene (18755-52-7) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 0 - 5 °C / Inert atmosphere 1.2: 0 °C / Inert atmosphere 2.1: sodium hydroxide; methanol / 2 h / 20 °C 3.1: potassium permanganate; acetic acid / water; acetone / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 2.33 h / -5 - 0 °C 1.2: 5 h / 0 °C 2.1: methanol; sodium hydroxide / 4 h / 25 - 30 °C 3.1: water; acetic acid; potassium permanganate / acetone / 7 h / 25 - 45 °C View Scheme

neophyl chloride (515-40-2) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 1-methyl-pyrrolidin-2-one / 160 - 165 °C 2.1: aluminum (III) chloride / dichloromethane / 0 - 5 °C / Inert atmosphere 2.2: 0 °C / Inert atmosphere 3.1: sodium hydroxide; methanol / 2 h / 20 °C 4.1: potassium permanganate; acetic acid / water; acetone / 0 - 20 °C View Scheme

2-(4-(4-Chloro-1-oxo-butyl))-phenyl-2-methyl propanyl acetate (169032-11-5) → 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol; sodium hydroxide / 4 h / 25 - 30 °C 2: water; acetic acid; potassium permanganate / acetone / 7 h / 25 - 45 °C View Scheme

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) → 2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid, methyl ester (154477-54-0)

Conditions	Yield
With hydrogenchloride; methanol at 40 - 45℃; for 7h;	95%

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) + ethanol (64-17-5) → 4-(4-chloro-1-oxobutyl)-α,α-dimethylbenzeneacetic acid ethyl ester (76811-97-7)

Conditions	Yield
With hydrogenchloride at 40 - 45℃; for 7h;	94.1%

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) + 2-amino-1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-3-phenylpropan-1-one → 2-(4-(cyclopropanecarbonyl)phenyl)-N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl)-2-methylpropanamide

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere;	82%

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) + sodium hydrogensulfite → 4-(4-iodo-1-oxobutyl)-α,α-dimethylphenylacetic acid (162096-55-1)

Conditions	Yield
In dichloromethane; trimethylsilyl iodide	12.6 g (77%)

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) → 4-(4-chloro-1-hydroxyl-butyl)-α,α-dimethyl phenyl acetic acid ethyl ester (1448311-89-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / 7 h / 40 - 45 °C 2: sodium tetrahydroborate / ethanol / 7 h / 25 - 30 °C View Scheme

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) → ethyl 4-[4[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetate (174483-06-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / 7 h / 40 - 45 °C 2: sodium tetrahydroborate / ethanol / 7 h / 25 - 30 °C 3: potassium hydrogencarbonate; potassium iodide / N,N-dimethyl-formamide / 16 h / Reflux View Scheme

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionic acid (162096-54-0) → fexofenadine (83799-24-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / 7 h / 40 - 45 °C 2: sodium tetrahydroborate / ethanol / 7 h / 25 - 30 °C 3: potassium hydrogencarbonate; potassium iodide / N,N-dimethyl-formamide / 16 h / Reflux 4: methanol; sodium hydroxide / 6 h / Reflux View Scheme

Upstream product

• 169280-24-4 2-(4-(1-Oxo-1-cyclopropanyl)-phenyl)-2-methyl propanyl acetate 
• 169280-26-6 2-(4-(1-Oxo-1-cyclopropanyl)-phenyl)-2-methylpropanol 
• 169280-06-2 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionitrile 
• 169280-22-2 2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionamide 
• 169032-11-5 2-(4-(4-Chloro-1-oxo-butyl))-phenyl-2-methyl propanyl acetate 
• 515-40-2 neophyl chloride 
• 18755-52-7 (2-acetoxy-1,1-dimethylethyl)benzene 
• 71-43-2 benzene 
• 64-17-5 ethanol 

Downstream Products

• 154477-54-0 2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid, methyl ester 
• 1448311-89-4 4-(4-chloro-1-hydroxyl-butyl)-α,α-dimethyl phenyl acetic acid ethyl ester 
• 174483-06-8 ethyl 4-[4[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetate 
• 83799-24-0 fexofenadine 
• 76811-97-7 4-(4-chloro-1-oxobutyl)-α,α-dimethylbenzeneacetic acid ethyl ester 
• 162096-55-1 4-(4-iodo-1-oxobutyl)-α,α-dimethylphenylacetic acid 

Relevant articles and documents

The synthesis of fexofenadine

This work proposes a new simple route for fexofenadine synthesis with low cost and easily obtainable raw materials. We use benzene and methallyl as starting reactants, applying steps of Friedel-Crafts alkylation reaction, hydrolysis, oxidation, esterification reaction, and reduction reaction to obtain the intermediate product, followed by N-alkylation reaction to obtain 4-{1-hydroxy-4-[4-(hydroxydiphenyl)-piperidine]butyl}-α, α-dimethylbenzene acetate. Then, the final product fexofenadine is obtained upon hydrolysis. In the synthesis process, we constantly optimize the reaction conditions such as reaction time, reaction temperature, solvent selection, and other factors, thus improving the final yield of the target product fexofenadine to 33.51 %.

Intermediates useful for the preparation of antihistaminic piperidine derivatives

The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula whereinW represents —C(=O)— or —CH(OH)—;R1 represents hydrogen or hydroxy;R2 represents hydrogen;R1 and R2 taken together form a second bond between the carbon atoms bearing R1 and R2;n is an integer of from 1 to 5;m is an integer 0 or 1;R3 is —COOH or —COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched each of A is hydrogen or hydroxy; andpharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R1 and R2 are taken together to form a second bond between the carbon atoms bearing R1 and R2 or where R1 represented hydroxy, m is an integer 0.

Intermediates useful for the preparation of antihistaminic piperidine derivatives

The present invention is related to a novel intermediates and processes which are useful in the preparation of certain antihistaminic piperidine derivatives of the formula wherein W represents —C(═O)— or —CH(OH)—; R1represents hydrogen or hydroxy; R2represents hydrogen; R1and R2taken together form a second bond between the carbon atoms bearing R1and R2; n is an integer of from 1 to 5; m is an integer 0 or 1; R3is —COOH or —COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; each of A is hydrogen or hydroxy; and pharmaceutically acceptable salts and individual optical isomers thereof, with the proviso that where R1and R2are taken together to form a second bond between the carbon atoms bearing R1and R2or where R1represented hydroxy, m is an integer 0.