41570-61-0

Basic information

• Product Name: Tulobuterol
• Synonyms: TULOBUTEROL;TULOBUTEROL BASE;alpha-[(tert-butylamino)methyl]-o-chlorobenzyl alcohol;TulobuterolHcl56776-01-3/Base;Tulobuterol(baseandorunspecifiedsalt);2-Chloro-a-[[(1,1-dimethylethyl)amino]methyl]benzenemethano;Benzenemethanol, 2-chloro-a-[[(1,1-dimethylethyl)amino]methyl]- (9CI);HN 078
• CAS NO: 41570-61-0
• Molecular Formula: C₁₂H₁₈ClNO
• Molecular Weight: 227.73
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Amines;Aromatics;API
• Mol File: 41570-61-0.mol
• Article Data: 10

Chemical Properties

• Melting Point: 89-91°C
• Boiling Point: 338.2 °C at 760 mmHg
• Flash Point: 158.3 °C
• Appearance: Crystalline Solid
• Density: 1.098 g/cm³
• Vapor Pressure: 3.9E-05mmHg at 25°C
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 13.62±0.20(Predicted)
• CAS DataBase Reference: Tulobuterol(CAS DataBase Reference)
• NIST Chemistry Reference: Tulobuterol(41570-61-0)
• EPA Substance Registry System: Tulobuterol(41570-61-0)

Safety Data

• Safety Statements: 24/25
• RTECS: DA4734170
• Hazardous Substances Data: 41570-61-0(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Uses

Different sources of media describe the Uses of 41570-61-0 differently. You can refer to the following data:
1. A ?adrenergic receptor agonist, related structurally to Terbutaline
2. Tulobuterol is a sympathomimetic drug used as a transdermal patch, increases normal diaphragm muscle strength.
3. A sympathomimetic drug used as a transdermal patch, increases normal diaphragm muscle strength. A β-adrenergic receptor agonist, related structurally to Terbutaline (T109750).

InChI:InChI=1/C12H18ClNO.ClH/c1-12(2,3)14-8-11(15)9-6-4-5-7-10(9)13;/h4-7,11,14-15H,8H2,1-3H3;1H

Synthetic route

1-(2-chlorophenyl)-2-hydroxyethanone (27993-71-1) + tert-butylamine (75-64-9) → tulobuterol (41570-61-0)

Conditions	Yield
With methanol; sodium tetrahydroborate at 15 - 20℃;	94.1%
Stage #1: 1-(2-chlorophenyl)-2-hydroxyethanone; tert-butylamine In 1,2-dichloro-ethane at 25℃; for 2h; Stage #2: With sodium tetrahydroborate In 1,2-dichloro-ethane at 0℃; for 2h;	73%

o-chlorostyrene oxide (62717-50-4) + tert-butylamine (75-64-9) → tulobuterol (41570-61-0)

Conditions	Yield
In methanol at 40 - 50℃; for 9h; Concentration;	93%
In water at 20℃; for 48h;	59%
In ethanol; toluene at 150℃; under 6000.6 - 6750.68 Torr; for 0.833333h; Flow reactor; regioselective reaction;	162 mg

2-Bromo-1-(2-chlorophenyl)ethan-1-ol (72702-57-9) + tert-butylamine (75-64-9) → tulobuterol (41570-61-0)

Conditions	Yield
In ethanol for 6h; Reflux; Large scale;	89%
In ethanol at 20 - 80℃; for 3h; Temperature;	85%
for 8h; Reflux; Inert atmosphere;	68%

1-(2-chlorophenyl)ethanone (2142-68-9) + tert-butylamine (75-64-9) → tulobuterol (41570-61-0)

Conditions	Yield
Stage #1: 1-(2-chlorophenyl)ethanone With N-Bromosuccinimide; toluene-4-sulfonic acid In dichloromethane for 6h; Reflux; Stage #2: tert-butylamine With magnesium sulfate In methanol at 30℃; for 4h; Inert atmosphere; Stage #3: With potassium borohydride In ethanol at -10 - 10℃; for 6.5h; Solvent; Reagent/catalyst; Temperature; Reflux;	79%

2-Chlorobenzyl alcohol (17849-38-6) → tulobuterol (41570-61-0)

Conditions

Yield

Multi-step reaction with 3 steps 1: sodium hypochlorite; potassium bromide; sodium hydrogencarbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / water; toluene / 0 °C / Flow reactor 2: sodium hydroxide; tetra-(n-butyl)ammonium iodide / water; toluene / 0.4 h / 90 °C / 750.08 - 1500.15 Torr / Flow reactor 3: ethanol; toluene / 0.83 h / 150 °C / 6000.6 - 6750.68 Torr / Flow reactor View Scheme

2'-chloro-sec-phenethyl alcohol (13524-04-4) → tulobuterol (41570-61-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydrogensulfate; hydroquinone / 3 h / 200 - 205 °C 2: sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid / dichloromethane / 6 h / Reflux 3: methanol / 9 h / 40 - 50 °C View Scheme

1-(2-chlorophenyl)ethanone (2142-68-9) → tulobuterol (41570-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iodine; dimethyl sulfoxide / 120 °C 2.1: 1,2-dichloro-ethane / 2 h / 25 °C 2.2: 2 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: bromine / water / 0.75 h / 20 °C / Large scale 2: potassium borohydride / water; ethanol / 0.25 h / 20 °C / Cooling with ice; Large scale 3: ethanol / 6 h / Reflux; Large scale View Scheme

2-chloro-benzaldehyde (89-98-5) → tulobuterol (41570-61-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium tert-butylate / dimethyl sulfoxide / 0.5 h / 5 - 20 °C 2: water / 48 h / 20 °C View Scheme

3-(tert-butyloxycarbonylamino)propionic acid (3303-84-2) + tulobuterol (41570-61-0) → C20H31ClN2O4

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃; for 3h;	98%

tulobuterol (41570-61-0) → Tulobuterol hydrochloride (56776-01-3)

Conditions	Yield
With hydrogenchloride In diethyl ether; isopropyl alcohol	91%

tulobuterol (41570-61-0) → β-alanyl-tulobuterol

Conditions	Yield
Multi-step reaction with 2 steps 1: dmap / dichloromethane / 3 h / 0 - 20 °C 2: hydrogenchloride / tetrahydrofuran; ethyl acetate / 2 h / 0 - 20 °C View Scheme

tulobuterol (41570-61-0) → tulobuterol + tulobuterol

Conditions	Yield
With ammonium acetate; triethylamine In water; acetonitrile pH=5;

Upstream product

• 89-98-5 2-chloro-benzaldehyde 
• 2142-68-9 1-(2-chlorophenyl)ethanone 
• 75-64-9 tert-butylamine 
• 72702-57-9 2-Bromo-1-(2-chlorophenyl)ethan-1-ol 
• 27993-71-1 1-(2-chlorophenyl)-2-hydroxyethanone 
• 13524-04-4 2'-chloro-sec-phenethyl alcohol 
• 17849-38-6 2-Chlorobenzyl alcohol 
• 62717-50-4 o-chlorostyrene oxide 

Downstream Products

• 56776-01-3 Tulobuterol hydrochloride 

Relevant articles and documents

Tulobuterol crystal form and preparation method thereof

The invention provides a tulobuterol crystal form and a preparation method thereof. The preparation method comprises the following steps of: dissolving tulobuterol in ethyl acetate and other good solvents, dropwisely adding n-heptane and other poor solvents into the system, filtering, taking the filter cake, and drying the filter cake to obtain the tulobuterol crystal form crystal. The crystal form is high in purity and good in stability, has superiority in process production, and is suitable for long-term storage in the preparation process.

Preparation method of tulobuterol

The invention provides a preparation method of tulobuterol. The technical problems of potential safety hazard, complicated post-treatment and the like in the existing method are solved. According to the method, a compound 1-(2-chlorphenyl)-2-tert-butylaminoethanol is synthesized from industrially available 2-chlorostyrene through a two-step reaction. The method is short in reaction step, mild in reaction condition, simple and convenient to operate, high in yield and good in application and development prospect, and can be used for preparing tulobuterol.

Method for synthesizing tulobuterol

The invention discloses a method for synthesizing tulobuterol. According to the method, 1-(2-chlorophenyl)-2-bromoethanone (compound 3) and 1-(2-chlorophenyl)-2,2-dibromoethanone (compound 10) can besimultaneously utilized to synthesize the tulobuterol. In an original route, the compound 10 is a by-product of synthesis of the compound 3, and about 10-15% of the compound 10 is not fully utilized.The method provided by the invention can improve the synthesis yield of the tulobuterol, is simple to operate, is environmentally friendly, is low in cost and is suitable for industrial production.