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(4S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(4-hydroxybenzene) propanoic acid, methyl ester, commonly known as Landiolol, is an important pharmaceutical intermediate that has gained significant attention in recent years.
As a derivative of the naturally occurring compound, monoethanolamine, Landiolol has shown promising results in various clinical trials, making it an important player in the development of new disease treatments.
In order to effectively synthesize Landiolol, however, it is crucial to follow proper instructions at every step of the process.
This article will provide a comprehensive guide on the synthesis of Landiolol, including the necessary starting materials, reagents, equipment, and reaction conditions.
Starting Materials
The synthesis of Landiolol requires several starting materials, including 2,2-dimethyl-1,3-dioxolan-4-one, para-oxybenzoic acid, methyl 4-amino-4-oxobutanoate, and acetic anhydride.
These materials can be obtained from various chemical suppliers or synthesized in-house using standard synthetic methods.
Reagents
The following reagents are required for the synthesis of Landiolol: triethylamine, pyridine, N,N-dimethylacetamide, sodium hydroxide, methanol, and Kinetic reagents (p-toluenesulfonic acid, N-methyl-2-pyrrolidinone, 2-propanol, water).
These reagents can also be obtained from chemical suppliers or synthesized in-house.
Equipment
The synthesis of Landiolol requires various pieces of equipment, including a reflux condenser, a magnetic stirrer, a thermometer, a separatory funnel, a Buchner funnel, and a high-speed centrifuge.
These equipment can be obtained from laboratory equipment suppliers or assembled in-house.
Reaction Conditions
The synthesis of Landiolol involves several stages, which require different reaction conditions.
The key stages of the synthesis are outlined below:
Stage 1: Synthesis of 2,2-dimethyl-1,3-dioxolan-4-one
To synthesize 2,2-dimethyl-1,3-dioxolan-4-one, 2,2-dimethyl-1,3-dioxane is treated with oxalyl chloride under anhydrous conditions.
The reaction is exothermic and should be carried out with caution.
The resulting reaction mixture is then treated with dry pyridine and poured into water.
The resulting solid is collected and dried to yield 2,2-dimethyl-1,3-dioxolan-4-one.
Stage 2: Synthesis of para-oxybenzoic acid
Para-oxybenzoic acid is synthesized by treating benzoic acid with o-toluenesulfonyl chloride in the presence of N,N-dimethylacetamide.
The reaction mixture is then poured into water and the resulting solid is collected and dried to yield para-oxybenzoic acid.
Stage 3: Synthesis of methyl 4-amino-4-oxobutanoate
To synthesize methyl 4-amino-4-oxobutanoate, methyl 4-aminobutanoate is treated with para-oxybenzoic acid in the presence of triethylamine.
The reaction mixture is then poured into water and the resulting solid is collected and dried to yield methyl 4-amino-4-oxobutanoate.
Stage 4: Synthesis of Landi