34381-68-5

Basic information

• Product Name: Acebutolol hydrochloride
• Synonyms: ACEBUTOLOL HCL;ACEBUTOLOL HYDROCHLORIDE;N-[3-ACETYL-4-(2-HYDROXY-3-[ISOPROPYLAMINO]PROPOXY)PHENYL]-BUTANAMIDE HYDROCHLORIDE;n-[3-acetyl-4-[2-hydroxy-3-[(isopropyl)amino]propoxy]phenyl]butyramide hydrochloride;3’-acetyl-4’-(2-hydroxy-3-(isopropylamino)propoxy)butyranilidehydrochloride;3’-acetyl-4’-(2-hydroxy-3-(isopropylamino)propoxy)-butyranilidmonohydrochl;acetobutololhydrochloride;dl-1-(2-acetyl-4-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropanehydroch
• CAS NO: 34381-68-5
• Molecular Formula: C₁₈H₂₈N₂O₄*ClH
• Molecular Weight: 372.89
• EINECS: 251-980-3
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Aromatics;AVODART
• Mol File: 34381-68-5.mol
• Article Data: 0

Chemical Properties

• Melting Point: 141-1430C
• Boiling Point: 564.1 °C at 760 mmHg
• Flash Point: 295 °C
• Appearance: Off-white powder
• Vapor Pressure: 1.45E-13mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Freely soluble in water and in ethanol (96 per cent), very slightly soluble in acetone and in methylene chloride.
• CAS DataBase Reference: Acebutolol hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Acebutolol hydrochloride(34381-68-5)
• EPA Substance Registry System: Acebutolol hydrochloride(34381-68-5)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36
• WGK Germany: 3
• RTECS: ES5235000
• Hazardous Substances Data: 34381-68-5(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Powder

Originator

Sectral ,May and Baker ,UK ,1975

Uses

5-alpha-reductase inhibitor

Definition

ChEBI: The hydrochloride salt of acebutolol, prepared using equimolar amounts of acebutolol and hydrogen chloride.

Manufacturing Process

Crude 5'-butyramido-2'-(2,3-epoxypropoxy)acetophenone (16 g), isopropylamine (20 g) and ethanol (100 ml) were heated together under reflux for 4 hours. The reaction mixture was concentrated under reduced pressure and the residual oil was dissolved in N hydrochloric acid. The acid solution was extracted with ethyl acetate, the ethyl acetate layers being discarded. The acidic solution was brought to pH 11 with 2 N aqueous sodium hydroxide solution and then extracted with chloroform. The dried chloroform extracts were concentrated under reduced pressure to give an oil which was crystallized from a mixture of ethanol and diethyl ether to give 5'-butyramido- 2'-(2-hydroxy-3-isopropylaminopropoxy)acetophenone (3 g), MP 119-123°C. Crude 5'-butyramido-2'-(2,3-epoxypropoxy)acetophenone used as starting material was prepared as follows: p-butyramidophenol (58 g; prepared according to Fierz-David and Kuster, Helv. Chim. Acta 1939,2282), acetyl chloride (25.4 g) and benzene (500 ml) were heated together under reflux until a solution formed (12 hours). This solution was cooled and treated with water. The benzene layer was separated and the aqueous layer was again extracted with benzene. The combined benzene extracts were dried and evaporated to dryness under reduced pressure to give p-butyramidophenyl acetate (38 g) as an off-white solid, MP 102-103°C. A mixture of p-butyramidophenyl acetate (38 g), aluminum chloride (80 g) and 1,1,2,2-tetrachloroethane (250 ml) was heated at 140°C for 3 hours. The reaction mixture was cooled and treated with iced water. The tetrachloroethane layer was separated and the aqueous layer was extracted with chloroform. The combined organic layers were extracted with 2 N aqueous sodium hydroxide and the alkaline solution was acidified to pH 5 with concentrated hydrochloric acid. The acidified solution was extracted with chloroform and the chloroform extract was dried and concentrated under reduced pressure to give 5'-butyramido-2'-hydroxyacetophenone (15.6 g), MP 114-117°C. A solution of 5'-butyramido-2'-hydroxyacetophenone (15.6 g) in ethanol (100 ml) was added to an ethanolic solution of sodium ethoxide which was prepared from sodium (1.62 g) and ethanol (100 ml). The resulting solution was evaporated to dryness under reduced pressure and dimethylformamide (100 ml) was added to the solid residue. Approximately 10 ml of dimethylformamide was removed by distillation under reduced pressure. Epichlorohydrin (25 ml) was added and the solution was heated at 100°C for 4 hours. The solution was concentrated under reduced pressure to give a residual oil which was treated with water to give a solid. The solid was dissolved in ethanol and the resulting solution was treated with charcoal, filtered and concentrated under reduced pressure to give crude 5'-butyramido- 2'-(2,3-epoxypropoxy)acetophenone (16 g), MP 110-116°C. The crude compound may be purified by recrystallization from ethyl acetate, after treatment with decolorizing charcoal, to give pure 5'-butyramido-2'-(2,3- epoxypropoxy)acetophenone, MP 136-138°C.

Brand name

Sectral (Dr. Reddy’s).

Therapeutic Function

beta-Adrenergic blocker

Safety Profile

Poison by ingestion, subcutaneous,intravenous, and intraperitoneal routes. An experimentalteratogen. Other experimental reproductive effects. Whenheated to decomposition it emits toxic fumes of NOx andHCl.

InChI:InChI=1/C18H28N2O4.ClH/c1-5-6-18(23)20-14-7-8-17(16(9-14)13(4)21)24-11-15(22)10-19-12(2)3;/h7-9,12,15,19,22H,5-6,10-11H2,1-4H3,(H,20,23);1H

Synthetic route

copper(II) choride dihydrate + acebutolol hydrochloride (34381-68-5) → [Cu2(N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide(-1H))2Cl2] (197433-18-4)

Conditions	Yield
With NaOH In methanol; water to soln. of ligand in MeOH equimolar amt. of aq. NaOH soln. added dropwise; to resulting soln. (pH 5-7) soln. of metal salt in MeOH added until the final metal ion:ligand:NaOH molar ratio was 1:2:2; mixt. stirred for20 min at room temp.; ppt. filtered; washed (MeOH/H2O, 1:1 v/v); dried (vac., P4O10) for several ds; elem. anal.;	60%

cobalt(II) chloride dihydrate + acebutolol hydrochloride (34381-68-5) → [Co(N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide(-1H))2(H2O)2] (796073-38-6)

Conditions	Yield
With NaOH In water; acetonitrile to soln. of ligand in H2O/MeCN (1/5 v/v) soln. of NaOH added dropwise; soln. of metal salt in MeCN/H2O (5/1, v/v) added; mixt. stirred for 30 min at room temp.; ppt. filtered; washed (MeCN/H2O, 1:1 v/v); dried (vac., P4O10) for several ds; elem. anal.;	55%

copper(II) choride dihydrate + acebutolol hydrochloride (34381-68-5) → [Cu(N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide)4]Cl2

Conditions	Yield
With NaOH In methanol; water to soln. of ligand in MeOH equimolar amt. of aq. NaOH soln. added dropwise; to resulting soln. (pH 5-7) soln. of metal salt in MeOH added until the final metal ion : ligand : NaOH molar ratio was 1:10:10; mixt. stirred for 2 h at room temp.; ppt. filtered; washed (MeOH/H2O, 1:1 v/v); dried (vac., P4O10) for several ds; elem. anal.;	50%

acebutolol hydrochloride (34381-68-5) → acetolol (57898-80-3)

Conditions	Yield
With hydrogenchloride In water at 100℃; for 5h;

Downstream Products

• 57898-80-3 acetolol 
• 197433-18-4 [Cu₂(N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide(-1H))2Cl₂] 
• 796073-38-6 [Co(N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]butanamide(-1H))2(H₂O)2]