alfa1-[[1,1-Dimethylethylamino]methyl]-4-hydroxy-1-(S),3-benzene dimethanol Hydrochlorid Struktur

alfa1-[[1,1-Dimethylethylamino]methyl]-4-hydroxy-1-(S),3-benzene dimethanol Hydrochlorid

Bezeichnung:alfa1-[[1,1-Dimethylethylamino]methyl]-4-hydroxy-1-(S),3-benzene dimethanol Hydrochlorid

Englisch Name:alfa1-[[1,1-Dimethylethylamino]methyl]-4-hydroxy-1-(S),3-benzene dimethanol Hydrochlorid

CBNumberCB4875349

SummenformelC13H22ClNO3

Molgewicht275.77168

alfa1-[[1,1-Dimethylethylamino]methyl]-4-hydroxy-1-(S),3-benzene dimethanol Hydrochlorid physikalisch-chemischer Eigenschaften

Schmelzpunkt	169-171°C
alpha	D20 -32.2° (c = 0.1 in water)
storage temp.	2-8°C
Löslichkeit	H2O: ≥15mg/mL
Aggregatzustand	powder
Farbe	white to tan
Optische Aktivität	[α]/D -25 to -35°, c = 0.1 in H2O

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22-37/38-41
S-Sätze:	26-39
WGK Germany	3
HS Code	2922504500

Gefahreninformationscode (GHS)

alfa1-[[1,1-Dimethylethylamino]methyl]-4-hydroxy-1-(S),3-benzene dimethanol Hydrochlorid Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Salbutamol is an agonist of the β₂-adrenergic receptor (β₂-AR; K_d = 759 nM in a radioligand binding assay using CHO cells expressing the human receptor). It is selective for β₂-ARs over β₁- and β₃-ARs (K_ds = 46.8 and 21.9 μM, respectively). Salbutamol (25-50 μg/kg, i.v.) reduces acetylcholine-induced bronchospasm in anesthetized guinea pigs. It also reduces response of bronchial muscle to efferent vagal stimulation in anesthetized cats and dogs when administered at doses ranging from 1 to 2.5 and 10 to 20 μg/kg, respectively. Nebulized salbutamol reduces transpulmonary pressure in recurrent airway obstruction-affected horses (EC₅₀ = 39.7 μg). Formulations containing salbutamol have been used in the treatment of asthma and chronic obstructive pulmonary disease (COPD).
Chemische Eigenschaften
Off-White Solid
Originator
Xopenex,Sepracor Inc.,USA
Verwenden
The R-enantiomer
Verwenden
Antiasthmatic
Verwenden
β2-agonist, bronchodilator
Verwenden
bronchodilator, tocolytic
Manufacturing Process
Preparation of 5-glyoxyloyl-salicylic acid methyl ester hydrate using aqueous HBr
To a 3-neck flask immersed in an oil bath containing a solution of 40 g (0.206 mole) methyl 5-acetylsalicylate in 6 ml methylene chloride is charged with 82 ml of isopropanol. The solution is distilled to remove excess methylene chloride. When the internal temperature reaches 77°C, 126 ml (1.77 mole or 8.6 equivalents) of DMSO is added to the reaction mixture and the temperature of the mixture is increased to a temperature of 85° to 90°C. Then 33 ml (0.29 mole or 1.4 equivalents) of HBr (aqueous, 48%) is added to the mixture over a period of 20 minutes (exothermic), and the bath temperature is maintained at 95° to 100°C. As the addition of HBr nears completion distillation is initiated and dimethysulfide and isopropanol are distilled off. The mixture is stirred and the volume of the distillate monitored. After distillation of 82 ml of solvent, 20 ml of isopropanol is added slowly to maintain a steady rate of distillation. After the reaction completed asdetermined by high performance liquid chromatography (HPLC), the reaction mixture is quenched with 70 ml of 2.4 N H2SO4, the temperature of the reaction mixture is allowed to drop to 75°C and residual isopropanol is distilled off under vacuum. After a total of 165 ml distillate is collected, the title compound begins to precipitate. A mixture of 30 ml of acetonitrile and 70 ml of water is added slowly at 75°C with stirring. After 30 minutes of stirring, the reaction mixture is cooled to 15°C over a period of 90 minutes to complete the precipitation. The reaction mixture is filtered and the cake is washed with three 300 ml portions of water. The cake is dried in a draft oven at 50°C for 16 hours to give 39.5 g of the title compound (85% yield).
Preparation of albuterol from 5-glyoxyloyl-salicylic acid methyl ester
To a solution of 5-glyoxyloylsalicylic acid methyl ester hydrate (50 g, 0.221 mol) in ethylene glycol diethyl ether, 440 mL is added tertiary butylamine (16.2 g, 0.221 mol) at room temperature. The resulting light orange solution is stirred for 5 min until a clear solution is formed. The clear solution is then heated to reflux. Water and DME are distilled off azeotropically. After a total of 200 ml of distillate are collected, the solution is cooled to 25°C. The reaction mixture is slowly added to a solution containing 49 mL (0.49 mol) of 10.0 M borane-dimethyl sulfide in 220 mL of ethylene glycol diethyl ether (DME) at 70°C. The resulting reaction mixture is further refluxed for 2.5 hrs. After the reaction is completed as monitored by HPLC, excess DME is removed via vacuum distillation. The residue containing complexes of boron and arylethanolamine is subsequently cooled to 0°C. Quenching of the residue with 300 mL methanol gives the methylborate of arylethanolamine. The borate is then removed by azeotropic distillation as trimethylborate, leaving behind the desired arylethanolamine in the reaction mixture. An additional 300 ml of methanol and acetic acid (85 mL) are added to ensure the complete removal of trimethylborate via vacuum distillation to near dryness. The residue containing the boron-free arylethanolamine is cooled to 25°C and concentrated sulfuric acid (10.4 g, 0.221 mole) in water (64 mL) is added following by 570 ml of isopropyl alcohol. Albuterol sulfate is precipitated out as a white solid. After the reaction mixture is stirred at room temperature for 12 hrs and 0°C for 30 min the albuterol sulfate is filtered, washed with isopropyl alcohol (two 50 mL portions) and dried at 50°C for 12 hrs to give 49.75 g of the title compound (78% yield) as racemate.
The optically pure albuterol may be prepared by resolving a mixture of enantiomers methyl benzoate albuterol precursors which prepared by procedures well known to persons skilled in the art. The starting material 4- benzyl albuterol is commercially available from Cipla (Bombay, India).
(-)-D-Dibenzoyltarta
Trademarks
Xopenex (Sepracor).
Therapeutic Function
Bronchodilator
Biochem/physiol Actions
Levalbuterol (levosalbutamol) is the more active isomer of albuterol. Levalbuterol is a β-adrenergic agonist; a bronchodilator used clinically to treat asthma and COPD..

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