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

Description

Tulobuterol is a sympathomimetic drug that functions as a β-adrenergic receptor agonist, structurally related to Terbutaline. It is a crystalline solid and is known for its ability to increase normal diaphragm muscle strength.

Uses

Used in Pharmaceutical Industry:
Tulobuterol is used as a transdermal patch for increasing normal diaphragm muscle strength. As a β-adrenergic receptor agonist, it helps in managing respiratory conditions by enhancing muscle strength and improving breathing efficiency.
Used in Respiratory Treatment:
Tulobuterol is used as a sympathomimetic drug for treating respiratory conditions, particularly those involving the diaphragm muscle. Its agonistic action on β-adrenergic receptors aids in improving muscle strength and overall respiratory function.

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

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

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.

Process for preparing beta-aminoalcohol from terminal olefin

The invention provides a method for preparing beta-aminoalcohol from terminal olefin. The method comprises the following steps: with the terminal olefin as a raw material, adding dibromohydantoin, conducting stirring, and then adding organic amine to obtain corresponding beta-aminoalcohol. The method has the advantages of mild conditions, easy operation, cheap raw materials, and wide application prospect.

Method for industrial production of tulobuterol

The invention discloses a method for industrial production of tulobuterol. The method comprises the following steps of 1, preparation of an intermediate II, wherein chloroacetophenone and an oxidant containing DMSO are added into a reaction kettle in sequence, a reaction is carried out for 1-1.5 hours under the condition of heat preservation, stirring is conducted until the reaction is completelyfinished, and through quenching, extraction, washing and concentration, the intermediate II is prepared; 2, preparation of a crude tulobuterol product, wherein the intermediate II, tert-butylamine, analcohol solvent and sodium borohydride are added into the reaction kettle in sequence and stirred, the reaction temperature is controlled, stirring is conducted until the reaction is completely finished, after concentration, extraction, washing and drying with a drying agent, filtration is conducted, and a filtrate is concentrated and recrystallized to obtain the crude tulobuterol product I; 3, refining of the tulobuterol, wherein the crude tulobuterol product I, an organic solvent and activated carbon for refinement of injection are recrystallized to obtain the refined tulobuterol. The industrial production method is green in reaction and simple in step and causes little pollution to the environment, the purity of the product is up to 99.95% or above, and the tulobuterol contains few impurities.