162358-09-0

Basic information

• Product Name: N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide
• Synonyms: 2-Acetoxymethyl-2-acetylamino-4-(4-octylphenyl)acetic Acid Butyl Ester;N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide;2-acetamido-2-(4-octylphenethyl)propane-1,3-diyl diacetate;Acetamide, N-[1,1-bis[(acetyloxy) methyl]-3-(4-octylphenyl)propyl]-;AcetaMide, N-[1,1-bis[(acetyloxy);Tricetyl fingolimod;2-Acetamido-2-(4-octylphenethyl);propane-1,3-diyl diacetate
• CAS NO: 162358-09-0
• Molecular Formula: C₂₅H₃₉NO₅
• Molecular Weight: 433.59
• EINECS: 1592732-453-0
• Product Categories: Aromatics Compounds;Aromatics
• Mol File: 162358-09-0.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 582.22 °C at 760 mmHg
• Flash Point: 305.916 °C
• Appearance: /
• Density: 1.043
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly)
• PKA: 14.68±0.46(Predicted)
• CAS DataBase Reference: N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide(162358-09-0)
• EPA Substance Registry System: N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide(162358-09-0)

Safety Data

• Hazardous Substances Data: 162358-09-0(Hazardous Substances Data)

Usage

Description

N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide is a complex organic compound derived from Diethyl 2-Acetamidomalonate (D443130), which serves as a versatile building block for the synthesis of various pharmaceutical and biologically active compounds. This off-white solid intermediate is specifically utilized in the preparation of Novobiocin (N888500) analogues, which are potential inhibitors of heat shock protein 90. Its unique chemical structure endows it with properties that make it a promising candidate for further research and development in the pharmaceutical industry.

Uses

Used in Pharmaceutical Industry:
N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide is used as an intermediate for the synthesis of pharmaceutical compounds, specifically for the preparation of Novobiocin analogues. These analogues have potential applications as inhibitors of heat shock protein 90, which plays a crucial role in the stabilization and refolding of proteins under stress conditions. Inhibition of this protein can have therapeutic implications in various diseases, including cancer and neurodegenerative disorders.
Used in Research and Development:
In the field of research and development, N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide serves as a valuable compound for exploring its potential applications in drug discovery. Its unique chemical structure allows researchers to investigate its interactions with various biological targets and evaluate its efficacy in modulating specific signaling pathways. This can lead to the development of novel therapeutic strategies and the identification of new drug candidates with improved pharmacological properties.
Used in Drug Synthesis and Design:
N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide is also used as a key component in the synthesis and design of new drugs. Its versatile chemical structure enables chemists to modify and optimize its properties, potentially leading to the development of more effective and targeted therapeutic agents. N-[1,1-Bis[(acetyloxy)methyl]-3-(4-octylphenyl)propyl]acetamide can be employed in the design of drugs with improved pharmacokinetics, reduced side effects, and enhanced selectivity for specific biological targets.

Synthetic route

2-acetamido-2-[2-(4-octanoylphenyl)ethyl]propane-1,3-diol diacetate (249289-07-4) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; for 2h;	95%
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃;	6.3 g

acetic anhydride (108-24-7) + N-(1-hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl) butan-2-yl) acetamide (249289-10-9) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
With pyridine at 20℃; for 16h; Acetylation;	8.25 g
Stage #1: N-(1-hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl) butan-2-yl) acetamide With pyridine Stage #2: acetic anhydride at 0 - 5℃;

n-octanoic acid chloride (111-64-8) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: 43 percent / AlCl3 / 1,2-dichloro-ethane / 3 h / 20 °C 2.1: triethylsilane; TFA / 1,2-dichloro-ethane / 3 h / 20 °C 3.1: 3.40 g / NaOMe; MeOH / 2 h / Heating 4.1: Et3N / CH2Cl2 / 1 h / 20 °C 5.1: 16.0 g / NaI / butan-2-one / 2 h / Heating 6.1: sodium ethoxide / ethanol / 0.5 h / 20 °C 6.2: 61 percent / ethanol / 3 h / 65 °C 7.1: LiAlH4 / tetrahydrofuran / 2 h / 20 °C 8.1: 8.25 g / pyridine / 16 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / 0.01 h / 0.25 - 0.3 °C 1.2: 0 h / 0.2 - 0.5 °C 2.1: sodium hydroxide / water; methanol / 1.5 h / 0.1 - 0.3 °C 3.1: palladium 10% on activated carbon; hydrogen / 0 h / 0.4 °C / Autoclave 4.1: sodium hydroxide / water; methanol / 0.2 - 0.3 °C 5.1: sodium iodide / butanone / 0.67 h / 0.8 - 0.85 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0.45 - 0.5 °C / Inert atmosphere 6.2: 0.4 - 0.45 °C / Inert atmosphere 7.1: calcium chloride / water; isopropyl alcohol / 0 h / 0.2 - 0.3 °C 7.2: 0.01 h / 0 - 0.5 °C 7.3: 0 h / 0.15 - 0.5 °C View Scheme
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 1,2-dichloro-ethane / 1.5 h / -15 - -10 °C / Inert atmosphere 1.2: 19 h / -15 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C View Scheme

acetic acid phenethyl ester (103-45-7) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: 43 percent / AlCl3 / 1,2-dichloro-ethane / 3 h / 20 °C 2.1: triethylsilane; TFA / 1,2-dichloro-ethane / 3 h / 20 °C 3.1: 3.40 g / NaOMe; MeOH / 2 h / Heating 4.1: Et3N / CH2Cl2 / 1 h / 20 °C 5.1: 16.0 g / NaI / butan-2-one / 2 h / Heating 6.1: sodium ethoxide / ethanol / 0.5 h / 20 °C 6.2: 61 percent / ethanol / 3 h / 65 °C 7.1: LiAlH4 / tetrahydrofuran / 2 h / 20 °C 8.1: 8.25 g / pyridine / 16 h / 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / 0.01 h / 0.25 - 0.3 °C 1.2: 0 h / 0.2 - 0.5 °C 2.1: sodium hydroxide / water; methanol / 1.5 h / 0.1 - 0.3 °C 3.1: palladium 10% on activated carbon; hydrogen / 0 h / 0.4 °C / Autoclave 4.1: sodium hydroxide / water; methanol / 0.2 - 0.3 °C 5.1: sodium iodide / butanone / 0.67 h / 0.8 - 0.85 °C 6.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0.45 - 0.5 °C / Inert atmosphere 6.2: 0.4 - 0.45 °C / Inert atmosphere 7.1: calcium chloride / water; isopropyl alcohol / 0 h / 0.2 - 0.3 °C 7.2: 0.01 h / 0 - 0.5 °C 7.3: 0 h / 0.15 - 0.5 °C View Scheme

2-acetylaminomalonic acid diethyl ester (1068-90-2) + (+-)-<2-bromo-ethyl>-phenyl-phosphinic acid ethyl ester → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium ethoxide / ethanol / 0.5 h / 20 °C 1.2: 61 percent / ethanol / 3 h / 65 °C 2.1: LiAlH4 / tetrahydrofuran / 2 h / 20 °C 3.1: 8.25 g / pyridine / 16 h / 20 °C View Scheme

diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate (162358-08-9) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran / 2 h / 20 °C 2: 8.25 g / pyridine / 16 h / 20 °C View Scheme
With pyridine; sodium borohydrid; acetic anhydride In methanol
Multi-step reaction with 2 steps 1.1: calcium acetate / isopropyl alcohol / 0.5 h / 10 - 15 °C 1.2: 10 - 15 °C 2.1: pyridine / 0.08 h 2.2: 0 - 5 °C View Scheme
Multi-step reaction with 2 steps 1.1: calcium acetate / isopropyl alcohol / 0.5 h / 10 - 15 °C 1.2: 10 - 15 °C 2.1: pyridine 2.2: 0 - 5 °C View Scheme

2-acetamido-1,3-diacetoxy-2-(2-phenylethyl)propane (162359-95-7) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aluminum (III) chloride; 1,2-dichloro-ethane / 18.5 h / 0 - 20 °C 2: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1.1: aluminum (III) chloride / 1,2-dichloro-ethane / 1.5 h / -15 - -10 °C / Inert atmosphere 1.2: 19 h / -15 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C View Scheme

1-phenyl-2-bromoethane (103-63-9) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: caesium carbonate / dimethyl sulfoxide / 6 h / 65 °C 2: sodium tetrahydroborate / methanol / 18 h / 0 - 20 °C 3: pyridine / 15 h / 20 °C 4: aluminum (III) chloride; 1,2-dichloro-ethane / 18.5 h / 0 - 20 °C 5: palladium 10% on activated carbon; hydrogen / ethanol / 2 h / 20 °C View Scheme

4'-(2-hydroxyethyl)octanophenone (219307-07-0) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: palladium 10% on activated carbon; hydrogen / 0 h / 0.4 °C / Autoclave 2.1: sodium hydroxide / water; methanol / 0.2 - 0.3 °C 3.1: sodium iodide / butanone / 0.67 h / 0.8 - 0.85 °C 4.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0.45 - 0.5 °C / Inert atmosphere 4.2: 0.4 - 0.45 °C / Inert atmosphere 5.1: calcium chloride / water; isopropyl alcohol / 0 h / 0.2 - 0.3 °C 5.2: 0.01 h / 0 - 0.5 °C 5.3: 0 h / 0.15 - 0.5 °C View Scheme

acetic anhydride (108-24-7) + diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate (162358-08-9) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Stage #1: diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate With calcium chloride In water; isopropyl alcohol at 0.2 - 0.3℃; for 0.00166667h; Stage #2: With sodium tetrahydroborate In water; isopropyl alcohol at 0 - 0.5℃; for 0.005h; Stage #3: acetic anhydride With dmap In dichloromethane at 0.15 - 0.5℃; for 0.002h; Solvent; Reagent/catalyst; Temperature;	75 g

acetyl chloride (75-36-5) + N-(1-hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl) butan-2-yl) acetamide (249289-10-9) → 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0)

Conditions	Yield
Stage #1: N-(1-hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl) butan-2-yl) acetamide With pyridine for 0.0833333h; Stage #2: acetyl chloride at 0 - 5℃;

2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0) → fingolimod hydrochloride

Conditions	Yield
Stage #1: 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate With methanol; water; lithium hydroxide Reflux; Stage #2: With hydrogenchloride In water; ethyl acetate; isopropyl alcohol at 50 - 70℃; for 0.5h;	86.03%
With hydrogenchloride In water at 100℃; for 1h;	79%
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 2 h / Reflux 2: hydrogenchloride / water; methanol / 0.5 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: lithium hydroxide / methanol / 2 h / Reflux 2: hydrogenchloride / isopropyl alcohol; ethyl acetate / 1 h / 70 - 80 °C View Scheme

2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0) → fingolimod (162359-55-9)

Conditions	Yield
With lithium hydroxide In methanol for 2h; Hydrolysis; Heating;
With sodium hydroxide In methanol; water for 2h; Reagent/catalyst; Reflux;	70 g
With lithium hydroxide In methanol for 2h; Reflux;

2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0) → acetic acid 2-acetoxymethyl-2-acetylamino-4-(3-bromo-4-octylphenyl)butyl ester (851039-26-4) + acetic acid 2-acetoxymethyl-2-acetylamino-4-(2-bromo-4-octylphenyl)butyl ester (851039-28-6)

Conditions	Yield
With N-Bromosuccinimide In acetic acid at 20℃; for 730.5h;

2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0) → C25H38FNO5 (1609282-73-6)

Conditions	Yield
With (S,S)-chloro[2,2'-[1,2-cyclohexanediylbis(nitrilomethylidyne)]bis-[4,6-bis(1,1-dimethylethyl)phenolato]](2-)-N,N',O,O'-manganese; iodosylbenzene; triethylamine tris(hydrogen fluoride) In acetonitrile at 50℃; Schlenk technique; Inert atmosphere;

2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate (162358-09-0) → C25H38(18)FNO5 (1609282-63-4)

Conditions	Yield
Stage #1: 2-acetamido-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol diacetate With (R,R)-Mn(salen)OTs; potassium carbonate In water; acetone at 20℃; for 0.0166667h; Stage #2: With iodosylbenzene In water; acetone at 50℃; for 0.166667h; regioselective reaction;

Upstream product

• 108-24-7 acetic anhydride 
• 249289-10-9 N-(1-hydroxy-2-(hydroxymethyl)-4-(4-octylphenyl) butan-2-yl) acetamide 
• 111-64-8 n-octanoic acid chloride 
• 103-45-7 acetic acid phenethyl ester 
• 1068-90-2 2-acetylaminomalonic acid diethyl ester 
• 162358-08-9 diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate 
• 162358-07-8 2-(4-octylphenyl)-1-iodoethane 
• 162358-05-6 2-(4-Octylphenyl)ethyl alcohol 
• 75-36-5 acetyl chloride 
• 219307-07-0 4'-(2-hydroxyethyl)octanophenone 
• 103-63-9 1-phenyl-2-bromoethane 
• 249289-07-4 2-acetamido-2-[2-(4-octanoylphenyl)ethyl]propane-1,3-diol diacetate 
• 162359-95-7 2-acetamido-1,3-diacetoxy-2-(2-phenylethyl)propane 
• 5463-92-3 2-acetylamino-2-phenylethylmalonic acid diethyl ester 

Downstream Products

• 851039-26-4 acetic acid 2-acetoxymethyl-2-acetylamino-4-(3-bromo-4-octylphenyl)butyl ester 
• 851039-28-6 acetic acid 2-acetoxymethyl-2-acetylamino-4-(2-bromo-4-octylphenyl)butyl ester 
• 1609282-73-6 C₂₅H₃₈FNO₅ 
• 1609282-63-4 C₂₅H₃₈⁽¹⁸⁾FNO₅ 
• 162359-55-9 fingolimod 

Relevant articles and documents

PROCESS FOR PREPARATION OF HIGHLY PURE FINGOLIMOD HYDROCHLORIDE

The present invention provides process for preparation of highly pure Fingolimod hydrochloride (I) having purity of greater than 99.8% (by HPLC),(I) without involving the use of column chromatographic purification in the entire process. Fingolimod hydrochloride (I) obtained by the process of present invention may be useful as active pharmaceutical ingredient in pharmaceutical compositions for the treatment of autoimmune related disorder including multiple sclerosis.

PROCESS FOR PREPARATION OF FINGOLIMOD

The present invention provides a process for preparation of fingolimod, a compound of Formula I or a pharmaceutically acceptable salt thereof, free of regioisomeric impurity compound of Formula IA

Production of 2-amino-2-[2-(4-C2-20-alkyl-phenyl)ethyl]propane-1,3-diols

Disclosed is a process for the production of 2-amino-2-[2-(4-C2-20-alkyl-phenyl)ethyl]propane-1,3-diols.