135271-47-5

Basic information

• Product Name: R-(-)-Salmeterol
• Synonyms: (R)-Salmeterol;1,3-Benzenedimethanol, 4-hydroxy-a1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-, (a1R)- (9CI);1,3-Benzenedimethanol, 4-hydroxy-a1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-, (R)-;R-(-)-Salmeterol;(R)-1-[3-(Hydroxymethyl)-4-hydroxyphenyl]-2-[[6-(4-phenylbutoxy)hexyl]amino]ethanol;(R)-4-Hydroxy-3-hydroxymethyl-α-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]benzenemethanol;2-(Hydroxymethyl)-4-[(R)-1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl]phenol;2-(Hydroxymethyl)-4-[(R)-2-[[6-(4-phenylbutoxy)hexyl]amino]-1-hydroxyethyl]phenol
• CAS NO: 135271-47-5
• Molecular Formula: C25H37NO4
• Molecular Weight: 415.57
• Mol File: 135271-47-5.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: R-(-)-Salmeterol(CAS DataBase Reference)
• NIST Chemistry Reference: R-(-)-Salmeterol(135271-47-5)
• EPA Substance Registry System: R-(-)-Salmeterol(135271-47-5)

Safety Data

• Hazardous Substances Data: 135271-47-5(Hazardous Substances Data)

Upstream product

• 629-03-8 1 ,6-dibromohexane 
• 3360-41-6 4-phenyl-butan-1-ol 
• 27475-14-5 2-benzyloxy-5-(2-bromoacetyl)benzoic acid methyl ester 
• 97664-58-9 D 2543 
• 94749-73-2 6-bromohexyl 4-phenylbutyl ether 
• 168412-89-3 1-azido-6-(4-phenylbutoxy)hexane 
• 97664-55-6 N-[6-(4-phenylbutoxy)hexyl]benzenemethanamine 
• 52113-69-6 6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxine 
• 208925-08-0 (2R)-hydroxy-2-(2,2-dimethyl-4H-1,3-benzodioxine-6-yl)-ethylamine 
• 208924-99-6 (R)-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-nitroethanol 
• 54030-32-9 4-hydroxy-3-(hydroxymethyl)benzaldehyde 
• 53412-47-8 3-(chloromethyl)-4-hydroxybenzaldehyde 
• 123-08-0 4-hydroxy-benzaldehyde 
• 2316-64-5 5-bromo-2-hydroxybenzyl alcohol 

Relevant articles and documents

Enantioselective synthesis of (R)-salmeterol employing an asymmetric Henry reaction as the key step

A practical synthesis of (R)-salmeterol has been accomplished from 3-bromo salicylaldehyde, which involved a Cu(II)-sparteine complex catalyzed asymmetric Henry reaction as the key step. (R)-Salmeterol can be obtained in 39% overall yield and 95% ee.

Structural isomers of saligenin-based β2-agonists: Synthesis and insight into the reaction mechanism

Salmeterol and albuterol are well-known β2-adenoreceptor agonists widely used in the treatment of inflammatory respiratory diseases, such as bronchial asthma and chronic obstructive pulmonary disease. Here we report the preparation of structural isomers of salmeterol and albuterol, which can be obtained from the same starting material as the corresponding β2-agonists, depending on the synthetic approach employed. Using 1D and various 2D NMR measurements, we determined that the structure of prepared isomers holds the β-aryl-β-aminoethanol moiety, in contrast to the α-aryl-β-aminoethanol moiety found in salmeterol and albuterol. We investigated the reaction of β-halohydrin and amines responsible for the formation of β-aryl-β-amino alcohol-both experimentally and using computational methods. The structure of β-halohydrin with the methyl salicylate moiety imposes the course of the reaction. The solvent plays a relevant, yet ambiguous role in the direction of the reaction, while the strength of the base influences the reaction yield and isomer ratio in a more evident way. Using computational methods, we have shown that the most probable reaction intermediate responsible for the formation of the unexpected isomer is the corresponding para-quinone methide, which can be formed due to phenol present in the methyl salicylate moiety. After successful preparation of albuterol and salmeterol isomers, we tested their inhibition potency to human acetylcholinesterase (AChE) and usual and atypical butyrylcholinesterase (BChE). Kinetic studies revealed that both isomers are low-potency reversible inhibitors of human cholinesterases.

Preparation method of salmeterol base

The invention discloses a preparation method of salmeterol. The method includes the following steps: carrying out a condensation reaction on a compound 2 and a compound 3 under an alkaline condition to obtain an intermediate 4; carrying out acidic hydrolysis to obtain an intermediate 5, and reducing the intermediate 5 to obtain an intermediate 6; and removing a benzyl group from the intermediate 6 by using palladium on carbon (Pd/C) to obtain a salmeterol base. The preparation method has the advantages of mild reaction conditions, simple post-treatment, low cost, high yield high product purity, and easiness in realization of industrialization.

Preparation method of Salmeterol Xinafoate

The invention discloses a preparation method of Salmeterol Xinafoate. The method comprises the following steps: condensation reaction of a compound 2 and a compound 3 under alkaline conditions to obtain an intermediate 4; acidic hydrolysis to obtain an intermediate 5, and reduction reaction of the intermediate 5 to obtain an intermediate 6; debenzylation of the intermediate 6 by use of palladium carbon (Pd / C) to obtain a salmeterol basic group; and salification from the salmeterol basic group and 1-hydroxy-2-naphthoic acid to obtain the Salmeterol Xinafoate. The preparation method has the advantages of mild reaction condition, simple post-treatment, low cost, high yield, high product purity and easy industrialization.

PROCESS FOR THE PREPARATION OF SALMETEROL XINAFOATE

The present invention relates to an improved process for the preparation of Salmeterol Xinafoate of Formula (I).

Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity

We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with Ki constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π–π interaction of salmeterol’s benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.

Synthesis method of R-salmeterol

The invention provides a synthesis method of R-salmeterol (V). The synthesis method comprises the following steps that a compound (I) and N-benzyl-6-(4-phenyl butoxy)-1-hexylamine take a reaction to obtain a compound (II); the compound (II) is hydrolyzed

PROCESS FOR THE PREPARATION OF SALMETEROL AND ITS INTERMEDIATES

The present invention discloses a process for the preparation of methyl 2-(benzyloxy)- 5-(2-bromoacetyl)benzoate (V), comprising: (d) benzylating methyl-5-acetyl-2-hydroxybenzoate (VIII) with benzyl chloride in the presence of a base and a catalyst in a suitable polar solvent to obtain 5-acetyl-2- benzyloxy benzoate (VII); (e) brominating methyl 5-acetyl-2-(benzyloxy)benzoate (VII) with a suitable brominating agent in one or more suitable' solvents in the presence of an acid catalyst to obtain methyl 2-(benzyloxy)-5-(2-bromoacetyl)benzoate V; (c) optionally, purifying the methyl 2-(benzyloxy)-5-(2-bromoacetyl)benzoate (V) in a suitable solvent; and (f) isolating the methyl 2-(benzyloxy)-5-(2-bromoacetyl)benzoate (V).

SUBSTITUTED ETHANOLAMINES

The present invention relates to new substituted ethanolamine adrenergic receptor modulators, pharmaceutical compositions thereof, and methods of use thereof.