13423-73-9

Basic information

• Product Name: 3,5-Diisopropyl-4-hydroxybenzoic acid
• Synonyms: 3,5-Bis(1-methylethyl)-4-hydroxybenzoic acid;4-Hydroxy-3,5-bis(1-Methylethyl)benzoic Acid;4-Hydroxy-3,5-diisopropylbenzoic Acid;Propofol 4-Carboxylic Acid;Propofol impurity N;Propofol EP Impurity N;Propofol－imA;4-hydroxy-3,5-di(propan-2-yl)benzoic acid
• CAS NO: 13423-73-9
• Molecular Formula: C₁₃H₁₈O₃
• Molecular Weight: 222.2802
• Product Categories: Aromatic Carboxylic Acids, Amides, Anilides, Anhydrides & Salts;Aromatics;Drug Analogues
• Mol File: 13423-73-9.mol
• Article Data: 11

Chemical Properties

• Melting Point: 146 °C
• Boiling Point: 343.5°Cat760mmHg
• Flash Point: 175.7°C
• Appearance: /
• Density: 1.108g/cm³
• Vapor Pressure: 2.69E-05mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Heated), Ethyl Acetate (Slightly), Methanol (Slightly)
• PKA: 4.65±0.10(Predicted)
• CAS DataBase Reference: 3,5-Diisopropyl-4-hydroxybenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Diisopropyl-4-hydroxybenzoic acid(13423-73-9)
• EPA Substance Registry System: 3,5-Diisopropyl-4-hydroxybenzoic acid(13423-73-9)

Safety Data

• Hazardous Substances Data: 13423-73-9(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 13423-73-9 differently. You can refer to the following data:
1. Propofol 4-Carboxylic acid is a related compound of Propofol (P829750), as an antioxidant.
2. Propofol 4-Carboxylic Acid (Propofol EP Impurity N) is a related compound of Propofol (P829750), as an antioxidant.

InChI:InChI=1/C13H18O3/c1-7(2)10-5-9(13(15)16)6-11(8(3)4)12(10)14/h5-8,14H,1-4H3,(H,15,16)

Synthetic route

isopropyl alcohol (67-63-0) + 4-hydroxy-benzoic acid (99-96-7) → 3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9)

Conditions	Yield
With sulfuric acid In water at 5 - 60℃; Large scale;	84%
at 40 - 60℃; Microwave irradiation;	78%
Stage #1: isopropyl alcohol; 4-hydroxy-benzoic acid With sulfuric acid In water at 15 - 65℃; for 4h; Friedel Crafts Alkylation; Stage #2: In water	74.6%

3,5-diisopropyl-4-hydroxybenzaldehyde (10537-86-7) → 3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9)

Conditions	Yield
With sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene In tetrahydrofuran; water; butan-1-ol at 20℃; for 16h;	68%

2,6-diisopropylphenol (2078-54-8) → 3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9)

Conditions	Yield
With hydrogenchloride; sodium methylate In N,N-dimethyl acetamide; water	23%
Multi-step reaction with 2 steps 1: acetic acid / water / 6 h / Reflux 2: sodium chlorite; sodium dihydrogenphosphate; 2-methyl-but-2-ene / water; tetrahydrofuran; butan-1-ol / 16 h / 20 °C View Scheme

carbon dioxide (124-38-9) + sodium-<2.6-diisopropyl-phenolate> → 3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9)

di-isopropyl ether (108-20-3) + 4-hydroxy-benzoic acid (99-96-7) → 3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9)

Conditions	Yield
With sulfuric acid at 10 - 65℃; Friedel-Crafts Alkylation;	120 g

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 2,6-diisopropylphenol (2078-54-8)

Conditions	Yield
Stage #1: 4-hydroxy-3,5-diisopropylbenzoic acid; sodium hydroxide In ethylene glycol at 140 - 145℃; for 7h; Inert atmosphere; Stage #2: With hydrogenchloride In water; ethylene glycol for 1h; pH=1 - 2;	93.5%
With decarboxylase at 25℃; for 15h; pH=6.5; Enzymatic reaction;	80.3%
With sodium hydroxide In 2-ethoxy-ethanol at 125 - 130℃; Large scale;	74%
Stage #1: 4-hydroxy-3,5-diisopropylbenzoic acid With sodium hydroxide In ethylene glycol at 140 - 145℃; Stage #2: With hydrogenchloride In water; ethylene glycol at 20℃; for 0.5h; pH=1 - 2;	53 g

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) + benzyl bromide (100-39-0) → benzyl 3,5-diisopropyl-4-hydroxybenzoate (160098-34-0)

Conditions	Yield
With potassium hydroxide In methanol; water; N,N-dimethyl-formamide; acetonitrile	79%

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) + hydroquinone (123-31-9) → C97H118O16

Conditions	Yield
Stage #1: 4-hydroxy-3,5-diisopropylbenzoic acid With toluene-4-sulfonic acid In para-xylene at 60℃; for 1.5h; Stage #2: hydroquinone In para-xylene at 110℃; for 16h;	61.5%

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) + allyl bromide (106-95-6) → 4-Allyloxy-3.5-diisopropyl-benzoesaeure (7192-38-3)

Conditions	Yield
With sodium methylate

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 4-Allyloxy-3.5-diisopropyl-benzoesaeure-aethylester (100347-71-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOMe 2: (i) SOCl2, (ii) /BRN= 1718733/, Py View Scheme

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 4-Allyloxy-3.5-diisopropyl-benzonitril (102075-37-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaOMe 2: (i) SOCl2, (ii) NH3 3: P2O5 / 165 °C View Scheme

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 4-Allyloxy-3.5-diisopropyl-benzamid (7192-63-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOMe 2: (i) SOCl2, (ii) NH3 View Scheme

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 3,3',5,5'-tetraisopropyl-[1,1'-biphenyl]-4,4'-diol (2416-95-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / 2-ethoxy-ethanol / 125 - 130 °C / Large scale 2.1: iron(III) chloride / water / 1 h / 90 °C 2.2: 1 h / 20 °C View Scheme

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 2-(1-methylethoxy)-1,3-bis(1-methylethyl)benzene (141214-18-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / 2-ethoxy-ethanol / 125 - 130 °C / Large scale 2: sodium hydroxide / N,N-dimethyl-formamide / 20 - 90 °C View Scheme

3,5-diisopropyl p-hydroxybenzoic acid (13423-73-9) → 2,6-diisopropyl-1,4-benzoquinone (1988-11-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / 2-ethoxy-ethanol / 125 - 130 °C / Large scale 2: ammonium cerium (IV) nitrate / acetonitrile / 1 h / 20 - 80 °C View Scheme

Upstream product

• 99-76-3 methyl 4-hydroxylbenzoate 
• 67-63-0 isopropyl alcohol 
• 10537-86-7 3,5-diisopropyl-4-hydroxybenzaldehyde 
• 108-20-3 di-isopropyl ether 
• 99-96-7 4-hydroxy-benzoic acid 
• 2078-54-8 2,6-diisopropylphenol 
• 124-38-9 carbon dioxide 

Downstream Products

• 160098-34-0 benzyl 3,5-diisopropyl-4-hydroxybenzoate 
• 2078-54-8 2,6-diisopropylphenol 
• 7192-63-4 4-Allyloxy-3.5-diisopropyl-benzamid 
• 102075-37-6 4-Allyloxy-3.5-diisopropyl-benzonitril 
• 100347-71-5 4-Allyloxy-3.5-diisopropyl-benzoesaeure-aethylester 
• 7192-38-3 4-Allyloxy-3.5-diisopropyl-benzoesaeure 
• 1988-11-0 2,6-diisopropyl-1,4-benzoquinone 
• 141214-18-8 2-(1-methylethoxy)-1,3-bis(1-methylethyl)benzene 
• 2416-95-7 3,3',5,5'-tetraisopropyl-[1,1'-biphenyl]-4,4'-diol 

Relevant articles and documents

SIMPLE MANUFACTURING AND PURIFICATION TECHNOLOGY FOR HIGH PURITY PROPOFOL

A process for manufacturing Pure Propofol with a purity of more than 99.90% is disclosed, said process comprising dissolving Crude Propofol in a solvent in which it is soluble to form a solution, treating the solution with aqueous alkali to form an aqueous alkali layer and a solvent layer, separating the aqueous alkali layer from the solvent layer using a phase separation technique, distilling off the solvent from the solvent layer, and distilling a residue of the solvent containing Propofol using steam or boiling water in a presence of dilute alkali and antioxidant like metabisulfite, under normal pressure or mild vacuum.

PROCESS FOR THE PREPARATION OF PROPOFOL

The present provides a simple, convenient and time-efficient process for the preparation of propofol. Particularly, the present invention provides an improved process for the preparation of propofol using a heterocyclic base for the decarboxylation reaction. The present invention provides a time-efficient process for the preparation of propofol with high yield and purity.

PHARMACOLOGICALLY ACTIVE COMPOUNDS

The present invention relates to compounds of formula (I) shown below: wherein Q is as defined herein. The compounds of formula (I) act as selective positive allosteric modulators of strychnine-sensitive alpha 1-glycine receptors. The present invention further relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of diseases or conditions in which strychnine-sensitive alpha 1-glycine receptor activity is implicated (such as, for example, chronic pain. The present invention also relates to processes for the preparation of these compounds and to pharmaceutical compositions comprising them.