136-47-0

Usage

InChI:InChI=1/C15H24N2O2.ClH/c1-4-5-10-16-14-8-6-13(7-9-14)15(18)19-12-11-17(2)3;/h6-9,16H,4-5,10-12H2,1-3H3;1H

Synthetic route

amethocaine (94-24-6) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
With hydrogenchloride In water; ethyl acetate	94%

2-(N,N-dimethylamino)ethanol (108-01-0) + ethyl 4-(N-butylamino)benzoate (94-32-6) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
With hydrogenchloride; sodium methylate In water at 130℃; for 8h;	85%

2-(N,N-dimethylamino)ethanol (108-01-0) + N-(n-butyl)-4-methoxycarbonylaniline (71839-12-8) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Stage #1: 2-(N,N-dimethylamino)ethanol; N-(n-butyl)-4-methoxycarbonylaniline With sodium methylate at 130℃; for 8h; Stage #2: With hydrogenchloride	83%

2-(N,N-dimethylamino)ethanol (108-01-0) + 4-amino-benzoic acid (150-13-0) + butyraldehyde (123-72-8) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Stage #1: 2-(N,N-dimethylamino)ethanol; 4-amino-benzoic acid; butyraldehyde With hydrogen at 40 - 45℃; under 2250.23 Torr; for 3h; Autoclave; Large scale; Stage #2: With dmap In 5,5-dimethyl-1,3-cyclohexadiene for 4h; Reflux; Large scale; Stage #3: With hydrogenchloride In ethanol; tert-butyl methyl ether; water at 45℃; pH=3 - 4; Reagent/catalyst; Temperature; Pressure; Solvent; Large scale;	75%

N-(4-ethoxycarbonylphenyl)butyramide (71134-92-4) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: dihydridocarbonyl(1,1,1-tris(diphenylphosphinomethyl)ethane)ruthenium(II) complex; hydrogen; toluene-4-sulfonic acid; boron trifluoride diethyl etherate / tetrahydrofuran / 20 h / 120 °C / 38002.6 Torr / Glovebox; Autoclave; Inert atmosphere 2: sodium methylate; hydrogenchloride / water / 8 h / 130 °C View Scheme

4-nitrobenzoic acid 2-(dimethylamino)ethyl ester (38152-22-6) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: iron; acetic acid / 8 h / 30 °C 2: potassium carbonate / N,N-dimethyl-formamide / 5 h / 50 °C 3: hydrogenchloride / ethyl acetate; water View Scheme

4-nitro-benzoyl chloride (122-04-3) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: dichloromethane / 2 h / 0 °C 2: iron; acetic acid / 8 h / 30 °C 3: potassium carbonate / N,N-dimethyl-formamide / 5 h / 50 °C 4: hydrogenchloride / ethyl acetate; water View Scheme

4-Bromobenzoic acid (586-76-5) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: copper / water; N,N-dimethyl-formamide / 25 h / 130 °C / Autoclave 2.1: sulfuric acid / 5,5-dimethyl-1,3-cyclohexadiene / Reflux 2.2: 20 - 25 °C / pH 3 - 4 View Scheme

2-(N,N-dimethylamino)ethanol (108-01-0) + 4-(N-butylamino)benzoic acid (4740-24-3) → tetracaine hydrochloride (136-47-0)

Conditions	Yield
Stage #1: 2-(N,N-dimethylamino)ethanol; 4-(N-butylamino)benzoic acid With sulfuric acid In 5,5-dimethyl-1,3-cyclohexadiene Reflux; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 20 - 25℃; pH=3 - 4;	22 g

tetracaine hydrochloride (136-47-0) + tetramethylammonium trifluoromethanethiolate → 2-(dimethylamino)ethyl 4-(butyl(trifluoromethyl)amino)benzoate

Conditions	Yield
Stage #1: tetracaine hydrochloride; tetramethylammonium trifluoromethanethiolate In acetonitrile at 20℃; Stage #2: With silver fluoride In acetonitrile at 50℃; for 4h;	97%

tetracaine hydrochloride (136-47-0) → 2-(dimethylamino)ethyl 4-(butylamino)-3-chlorobenzoate (1344028-77-8)

Conditions	Yield
With N-chloro-succinimide In acetonitrile for 24h; Reflux;	75%
With N-chloro-succinimide In acetonitrile for 24h; Reflux;	75%

tetracaine hydrochloride (136-47-0) → 2-(N,N-dimethylamino)ethanol (108-01-0) + 4-(N-butylamino)benzoic acid (4740-24-3)

Conditions	Yield
With water Thermodynamic data; Rate constant; var. pH-values;

tetracaine hydrochloride (136-47-0) + β‐cyclodextrin (7585-39-9) → 2-dimethylaminoethyl 4-(n-butylamino)benzoate β-cyclodextrin (150398-16-6)

Conditions	Yield
aq. buffer;

tetracaine hydrochloride (136-47-0) + cyclomaltooctaose (17465-86-0) → 2-dimethylaminoethyl 4-(n-butylamino)benzoate γ-cyclodextrin (150398-18-8)

Conditions	Yield
aq. buffer;

tetracaine hydrochloride (136-47-0) + alpha cyclodextrin (10016-20-3) → 2-dimethylaminoethyl 4-(n-butylamino)benzoate α-cyclodextrin (150398-13-3)

Conditions	Yield
aq. buffer;

bovine β-lactoglobulin isoform A + tetracaine hydrochloride (136-47-0) → 1:1 complex of bovine β-lactoglobulin isoform A and tetracaine hydrochloride

Conditions	Yield
at 25℃; pH=7.5;

Upstream product

• 71134-92-4 N-(4-ethoxycarbonylphenyl)butyramide 
• 108-01-0 2-(N,N-dimethylamino)ethanol 
• 94-32-6 ethyl 4-(N-butylamino)benzoate 
• 38152-22-6 4-nitrobenzoic acid 2-(dimethylamino)ethyl ester 
• 122-04-3 4-nitro-benzoyl chloride 
• 94-24-6 amethocaine 
• 586-76-5 4-Bromobenzoic acid 
• 4740-24-3 4-(N-butylamino)benzoic acid 
• 71839-12-8 N-(n-butyl)-4-methoxycarbonylaniline 
• 150-13-0 4-amino-benzoic acid 
• 123-72-8 butyraldehyde 

Downstream Products

• 108-01-0 2-(N,N-dimethylamino)ethanol 
• 4740-24-3 4-(N-butylamino)benzoic acid 
• 150398-16-6 2-dimethylaminoethyl 4-(n-butylamino)benzoate β-cyclodextrin 
• 150398-18-8 2-dimethylaminoethyl 4-(n-butylamino)benzoate γ-cyclodextrin 
• 150398-13-3 2-dimethylaminoethyl 4-(n-butylamino)benzoate α-cyclodextrin 
• 1344028-77-8 2-(dimethylamino)ethyl 4-(butylamino)-3-chlorobenzoate 

Relevant academic research and scientific papers

Preparation method of tetracaine hydrochloride

The invention discloses a preparation method of tetracaine hydrochloride. The preparation method of the tetracaine hydrochloride comprises the steps of a first step reaction of p-aminobenzoic acid andN-butyraldehyde, a second step reaction of a first step reaction product and N,N-dimethyl ethanolamine of and a salt forming reaction of the third step, wherein the first step reaction is carried outin the presence of N,N-dimethyl ethanolamine, a system after the first reaction directly performs the second reaction without concentration. The N,N-dimethyl ethanolamine is adopted to replace alcohol solvent in the aldehyde-amine reaction, solvent switching before a second esterification reaction is eliminated, and the possibility of generating impurities due to incomplete removal of the alcoholsolvent is eliminated, so that the content of a final product is effectively improved.

B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane

The first B(C6F5)3-catalyzed deoxygenative reduction of amides into the corresponding amines with readily accessible and stable ammonia borane (AB) as a reducing agent under mild reaction conditions is reported. This metal-free protocol provides facile access to a wide range of structurally diverse amine products in good to excellent yields, and various functional groups including those that are reduction-sensitive were well tolerated. This new method is also applicable to chiral amide substrates without erosion of the enantiomeric purity. The role of BF3 ? OEt2 co-catalyst in this reaction is to activate the amide carbonyl group via the in situ formation of an amide-boron adduct. (Figure presented.).

Method for preparing tetracaine hydrochloride

The invention discloses a method for preparing tetracaine hydrochloride. The method comprises the following steps: (1) preparing 4-n-butyl aminobenzoic acid, namely adding a solvent, 4-halogen-benzoicacid, n-butylamine and copper catalyst into a high pressure reactor to obtain the 4-n-butyl aminobenzoic acid; (2) preparing tetracaine, namely adding the 4-n-butyl aminobenzoic acid prepared in thestep (1), N,N-dimethylethanolamine, concentrated sulfuric acid and a solvent into a reaction bottle, heating, refluxing and diverting to obtain the tetracaine; and (3) preparing tetracaine hydrochloride, namely reacting the tetracaine prepared in the step (2) with concentrated hydrochloric acid in a solvent at a certain temperature to obtain the tetracaine hydrochloride. The method has the advantages that 1, the copper catalyst has smaller toxicity, is low in price and easily available while the copper catalyst is much safer, and the cost for raw materials and operation can be greatly reduced;2, the raw materials are easily available, the reaction has few steps, the intermediate reacting process can be easily controlled, few byproduct is generated, and large-scale production is easy to implement; and 3, the product has high purity and high total yield.

Preparation method of tetracaine hydrochloride

The invention relates to the technical field of preparation method of tetracaine hydrochloride. The preparation method comprises the preparation steps: carrying out a reaction of p-nitrobenzoyl chloride (2) and 2-dimethylamino-1-ethanol (3) to generate p-nitrobenzoic acid-2-dimethylamino ethyl (4), reducing the compound (3) to obtain p-aminobenzoic acid-2-dimethylamino ethyl (4), generating pontocaine (7) from a compound (5) and 1-bromobutane (6) under alkaline conditions, and finally carrying out a reaction of the pontocaine (7) with HCl to generate tetracaine hydrochloride (1).

Boron Lewis Acid Promoted Ruthenium-Catalyzed Hydrogenation of Amides: An Efficient Approach to Secondary Amines

The hydrogenation of amides to amines has been developed by using the catalyst [Ru(H)2(CO)(Triphos)] (Triphos=1,1,1-tri(diphenylphosphinomethyl)ethane) and catalytic boron Lewis acids such as B(C6F5)3 or BF3?Et2O as additives. The reaction provides an efficient method for the preparation of secondary amines from amides in good yields with high selectivity.