79874-76-3

Basic information

• Product Name: Delmopinol
• Synonyms: Delmopinol;(+-)-3-(4-Propylheptyl)-4-morpholineethanol;Decapinol;(Rs)-2-(3-(4-propylheptyl)morpholino)ethanol;4-Morpholineethanol, 3-(4-propylheptyl)-, ( -)-;Decapinolum;Delmopinolum;Delmopinolum [inn-latin]
• CAS NO: 79874-76-3
• Molecular Formula: C₁₆H₃₃NO₂
• Molecular Weight: 271.44
• Mol File: 79874-76-3.mol

Chemical Properties

• Boiling Point: 374.576 °C at 760 mmHg
• Flash Point: 180.338 °C
• Appearance: /
• Density: 0.924 g/cm³
• Vapor Pressure: 3.84E-07mmHg at 25°C
• Refractive Index: 1.462
• CAS DataBase Reference: Delmopinol(CAS DataBase Reference)
• NIST Chemistry Reference: Delmopinol(79874-76-3)
• EPA Substance Registry System: Delmopinol(79874-76-3)

Safety Data

• Hazardous Substances Data: 79874-76-3(Hazardous Substances Data)

Usage

Uses

Used in Dental Care Industry:
Delmopinol is used as an active ingredient in dental care products for its ability to promote acid adaptation and reduce acid production in dental plaque biofilms. This helps in maintaining oral health and preventing dental caries.
Used in Therapeutic Applications:
Delmopinol is used as a therapeutic agent for its fluoride content, which aids in strengthening tooth enamel and providing protection against tooth decay. Its effect on acid adaptation and acid production also contributes to its therapeutic potential in dental care.
Used in Biological Studies:
Delmopinol is used in biological research to study the mechanisms of acid adaptation and acid production in dental plaque biofilms. This helps in understanding the factors that contribute to dental caries and the development of effective preventive measures.

InChI:InChI=1/C16H33NO2/c1-3-6-15(7-4-2)8-5-9-16-14-19-13-11-17(16)10-12-18/h15-16,18H,3-14H2,1-2H3

Synthetic route

methanesulfonic acid 1-[2-(2,2-dimethyl-oxazolidin-3-yl)-ethoxymethyl]-5-propyl-octyl ester → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Stage #1: methanesulfonic acid 1-[2-(2,2-dimethyl-oxazolidin-3-yl)-ethoxymethyl]-5-propyl-octyl ester With water at 95℃; for 17h; Stage #2: With sulfuric acid; water In toluene pH=1; Stage #3: With sodium hydroxide; water at 60℃; for 0.166667h; pH=14; Product distribution / selectivity;	89%

3-(4-propyl-heptyl)morpholine (79874-63-8) + 2-chloro-ethanol (107-07-3) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Stage #1: 3-(4-propyl-heptyl)morpholine; 2-chloro-ethanol With potassium iodide In ethanol for 5h; Reflux; Stage #2: With potassium hydroxide In ethanol for 11h; Reflux;	70.7%

methanesulfonic acid 1-[2-(2-ethyl-oxazolidin-3-yl)-ethoxymethyl]-5-propyl-octyl ester → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
With water at 95℃; for 17h; Product distribution / selectivity;	70%

3-(4-propyl-heptyl)morpholine (79874-63-8) + 1-chloroethanol (594-01-4) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
With potassium hydroxide; potassium iodide In ethanol; water

C10H21BrMg + oxazolidin[2,3-c]morpholine (937717-10-7) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Stage #1: C10H21BrMg; oxazolidin[2,3-c]morpholine In tetrahydrofuran; toluene at 20℃; for 0.5h; Stage #2: With ammonium chloride In tetrahydrofuran; water; toluene at 40℃;

1-chloro-4-propylhept-3-ene → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ethyl bromide; magnesium / tetrahydrofuran / 3 h / 45 °C / Reflux 1.2: 1.5 h / 20 - 25 °C 2.1: 5%-palladium/activated carbon; hydrogen / methanol / 40 °C / 3750.38 Torr View Scheme
Multi-step reaction with 2 steps 1.1: lithium hydride / tetrahydrofuran / 20 °C / Reflux 1.2: 20 °C / Reflux 2.1: hydrogen; 5%-palladium/activated carbon / methanol / 30 °C / 2250.23 Torr View Scheme

2-(3-(4-propylhept-3-en-1-yl)morpholino)ethan-1-ol → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In methanol at 40℃; under 3750.38 Torr;	323 g

oxazolidin[2,3-c]morpholine (937717-10-7) + 1-chloro-4-propylheptane → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Stage #1: 1-chloro-4-propylheptane With ethyl bromide; magnesium In tetrahydrofuran at 60 - 65℃; for 3.5h; Stage #2: oxazolidin[2,3-c]morpholine In tetrahydrofuran; toluene at 0 - 5℃;	79.2 g

4-cyclopropylheptan-4-ol (57583-50-3) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water / 10 h / 30 - 40 °C / Large scale 2.1: hydrogen; platinum on carbon / methanol / 30 °C / 2250.23 Torr 3.1: ethyl bromide; magnesium / tetrahydrofuran / 3.5 h / 60 - 65 °C 3.2: 0 - 5 °C View Scheme
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water / 10 h / 20 - 40 °C / Large scale 2.1: ethyl bromide; magnesium / tetrahydrofuran / 3 h / 45 °C / Reflux 2.2: 1.5 h / 20 - 25 °C 3.1: 5%-palladium/activated carbon; hydrogen / methanol / 40 °C / 3750.38 Torr View Scheme
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water / 10 h / 20 - 40 °C / Large scale 2.1: lithium hydride / tetrahydrofuran / 20 °C / Reflux 2.2: 20 °C / Reflux 3.1: hydrogen; 5%-palladium/activated carbon / methanol / 30 °C / 2250.23 Torr View Scheme

4-(2-hydroxyethyl)morpholin-3-one (41036-01-5) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: lithium hydride / tetrahydrofuran / 20 °C / Reflux 1.2: 20 °C / Reflux 2.1: hydrogen; 5%-palladium/activated carbon / methanol / 30 °C / 2250.23 Torr View Scheme

8a-(4-propylhept-3-en-1-yl)hexahydrooxazolo[2,3-c][1,4]oxazine → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
With 5%-palladium/activated carbon; hydrogen In methanol at 30℃; under 2250.23 Torr;	116.5 g

4-heptanone (123-19-3) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 12 h / 25 - 30 °C 2.1: sodium tungstate (VI) dihydrate; dihydrogen peroxide / methanol; ethanol / 18 h / 50 - 60 °C 3.1: toluene-4-sulfonic acid; hydrogen; palladium on activated charcoal / isopropyl alcohol / 15 h / 70 - 80 °C / 22502.3 Torr / Autoclave 4.1: Triphenylphosphine oxide; trifluoromethylsulfonic anhydride; sodium tetrahydroborate / dichloromethane / 12.5 h / 0 - 25 °C / Inert atmosphere 5.1: potassium iodide / ethanol / 5 h / Reflux 5.2: 11 h / Reflux View Scheme

4-hydroxy-4-propyl-1-heptene (62108-07-0) → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: sodium tungstate (VI) dihydrate; dihydrogen peroxide / methanol; ethanol / 18 h / 50 - 60 °C 2.1: toluene-4-sulfonic acid; hydrogen; palladium on activated charcoal / isopropyl alcohol / 15 h / 70 - 80 °C / 22502.3 Torr / Autoclave 3.1: Triphenylphosphine oxide; trifluoromethylsulfonic anhydride; sodium tetrahydroborate / dichloromethane / 12.5 h / 0 - 25 °C / Inert atmosphere 4.1: potassium iodide / ethanol / 5 h / Reflux 4.2: 11 h / Reflux View Scheme

C14H27NO3 → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid; hydrogen; palladium on activated charcoal / isopropyl alcohol / 15 h / 70 - 80 °C / 22502.3 Torr / Autoclave 2.1: Triphenylphosphine oxide; trifluoromethylsulfonic anhydride; sodium tetrahydroborate / dichloromethane / 12.5 h / 0 - 25 °C / Inert atmosphere 3.1: potassium iodide / ethanol / 5 h / Reflux 3.2: 11 h / Reflux View Scheme

C14H29NO2 → 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Triphenylphosphine oxide; trifluoromethylsulfonic anhydride; sodium tetrahydroborate / dichloromethane / 12.5 h / 0 - 25 °C / Inert atmosphere 2.1: potassium iodide / ethanol / 5 h / Reflux 2.2: 11 h / Reflux View Scheme

3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3) → 2-(3-(4-propylheptyl)morpholino)ethan-1-ol hydrochloride

Conditions	Yield
With hydrogenchloride In Isopropyl acetate at 0℃;	84%

3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3) → rac-4-(2-hydroxyethyl)-3-(4-propylheptyl) morpholine hydrochloride (98092-92-3)

Conditions	Yield
With hydrogenchloride In dibutyl ether; water; ethyl acetate at 0 - 60℃; for 3h; Product distribution / selectivity;	67%
With hydrogenchloride In water at 0 - 60℃; for 4h; Product distribution / selectivity;	50%
With hydrogenchloride In water; 4-methyl-2-pentanone at 0 - 60℃; for 2h;
With hydrogenchloride In Isopropyl acetate at 0℃;	93.5 g

3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3) → delmopinol sodium salt

Conditions	Yield
With sodium hydride In toluene; mineral oil at 0 - 25℃; for 2.16h; Reagent/catalyst; Temperature; Solvent;	58.9%

citric acid (77-92-9) + 3-(4-propyl-heptyl)-4-(2-hydroxyethyl)-morpholine (79874-76-3) → 2-(3-(4-propylheptyl)morpholino)ethan-1-ol citrate

Conditions	Yield
In ethyl acetate; isopropyl alcohol at 20 - 25℃; Temperature; Solvent;	351.9 g

Upstream product

• 79874-63-8 3-(4-propyl-heptyl)morpholine 
• 594-01-4 1-chloroethanol 
• 57583-50-3 4-cyclopropylheptan-4-ol 
• 41036-01-5 4-(2-hydroxyethyl)morpholin-3-one 
• 107-07-3 2-chloro-ethanol 
• 123-19-3 4-heptanone 
• 62108-07-0 4-hydroxy-4-propyl-1-heptene 
• 937717-10-7 oxazolidin[2,3-c]morpholine 

Downstream Products

• 98092-92-3 rac-4-(2-hydroxyethyl)-3-(4-propylheptyl) morpholine hydrochloride 

Relevant articles and documents

METHODS OF MAKING DELMOPINOL AND SALTS THEREOF

Disclosed are methods of making delmopinol and delmopinol salts (e.g., delmopinol metal salts, such as, for example, delmopinol calcium salts, delmopinol sodium salts, delmopinol potassium salts, and/or delmopinol magnesium salts). Delmopinol has structure (I) and a salt of delmopinol has structure (II).

METHOD FOR THE MANUFACTURING OF 2-(3-(ALKYL AND ALKENYL)MORPHOLINO)-ETHAN-1-OLS

The present invention relates to a method for the manufacture of 2-(3-(alkyl or alkenyl)morpholino)-ethan-1-ols by reduction of 8a-(alkyl and alkenyl)hexahydrooxazolo[2,3-c][1,4]oxazines encompassing a process for producing 2-(3-(4-propylheptyl)morpholino)ethan-1-ol with the INN name delmopinol. The invention also relates to 1-chloro-4-propylhept-3-ene, 1-iodo-4-propylhept-3-ene, 8a-(4-5 propylheptyl)hexahydrooxazolo[2,3-c][1,4]oxazine, 8a-(4-propylhept-3-en-1-yl)hexahydrooxazolo[2,3-c][1,4]oxazine and 2-(3-(4-propylhept-3-en-1-yl)morpholino)ethan-1-ol which are intermediates in the delmopinol process.

METHOD FOR THE MANUFACTURING OF DELMOPINOL INTERMEDIATES

The present invention relates to a new process for producing intermediates useful in the manufacture of 2-(3-(4-propylheptyl)morpholino)ethan-l-ol. The invention also relates to intermediates l-chloro-4-propylhept-3-ene and l-iodo-4-propylhept-3-ene.

METHOD FOR THE MANUFACTURING OF DELMOPINOL

The present invention relates to a new process for producing 2-(3-(4-propylheptyl)morpholino)ethan-1-ol with the INN name Delmopinol. The invention also relates to three key intermediates 1-chloro-4- propylhept-3-ene, 1-iodo-4-propylhept-3-ene and 2-(3-(4-propylhept-3-en-1-yl)morpholino)ethan-1-ol.

PROCESS FOR THE PREPARATION OF DELMOPINOL AND DERIVATIVES THEREOF

A process for the preparation of delmopinol (3-(4-propylheptyl)-4-morpholinethanol) or a derivative or a pharmaceutically acceptable salt, or a solvate thereof, including an hydrate, comprises reacting oxazolidin [2, 3-c] morpholine and a grignard reagent, and optionally converting the delmopinol (or derivative) free base into a pharmaceutically acceptable salt. The oxazolidin [2, 3-c] morpholine and the grignard reagent are useful as intermediates in the production process.

PREPARATION OF DELMOPINOL

It comprises a process for the production of delmopinol or a pharmaceutically acceptable salt and/or a solvate thereof, by subjecting the compound of formula (II) where R1 and R2 are the same or different, independently selected from the group consisting of H, (C1-C6) alkyl or, alternatively, R1 and R2 form, together with the carbon atom to which they are attached, a (C5-C6) cycloalkyl radical; and R3 is a radical selected from the group consisting of CF3, (C1-C4) alkyl, phenyl, and phenyl mono- ordisubstituted by a radical selected from the group consisting of (C1-C4)-alkyl, halogen and nitro to a deprotection and cyclisation reaction. The process is useful to prepare delmopinol or its salts on an industrial scale. The compound of formula (II) is new and also forms part of the present invention, as well as its preparation process and other new intermediates of said preparation process. .

Substituted isoxazolidines and isoxazolines as intermediates for delimopinal

The invention concerns intermediates having the formula STR1 wherein R is 2-propylpentyl optionally with one, two or three internal unsaturated bonds, or 2-substituted-2-propylpentyl optionally with one or two internal unsaturated bonds wherein the 2-substituent is a leaving group.