56718-76-4

Basic information

• Product Name: rac 1-Chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propanol
• Synonyms: rac 1-Chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propanol;(+/-)1-chloro-2-hydroxy-3-[4-(2-Methoxyethyl)phenoxy]-propane;Metoprolol Related CoMpound B;Metoprolol Related Compound B (100 mg) ((+/-)1-Chloro-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]-propane);Metoprolol Tartrate USP RC B;1-Chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propanol;Metoprolol USP RC B;Metoprolol USP Related Compound B
• CAS NO: 56718-76-4
• Molecular Formula: C₁₂H₁₇ClO₃
• Molecular Weight: 244.71458
• Product Categories: Aromatics;Intermediates
• Mol File: 56718-76-4.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 364.5°C at 760 mmHg
• Flash Point: 174.2°C
• Appearance: /
• Density: 1.157g/cm³
• Vapor Pressure: 5.95E-06mmHg at 25°C
• Refractive Index: 1.521
• Storage Temp.: Refrigerator, under inert atmosphere
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 13.12±0.20(Predicted)
• BRN: 7622429
• CAS DataBase Reference: rac 1-Chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propanol(CAS DataBase Reference)
• NIST Chemistry Reference: rac 1-Chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propanol(56718-76-4)
• EPA Substance Registry System: rac 1-Chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propanol(56718-76-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Hazardous Substances Data: 56718-76-4(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 56718-76-4 differently. You can refer to the following data:
1. An intermediate for the synthesis of -chlorohydrins and -chloroamines.
2. An intermediate for the synthesis of β-chlorohydrins and β-chloroamines. An impurity found in metoprolol
3. An intermediate for the synthesis of β-chlorohydrins and β-chloroamines. An impurity found in metoprolol. Metroprolol USP Related Compound B.

InChI:InChI=1/C12H17ClO3/c1-15-7-6-10-2-4-12(5-3-10)16-9-11(14)8-13/h2-5,11,14H,6-9H2,1H3

Synthetic route

2-[4-(2'-methoxyethyl)phenoxymethyl]oxirane (56718-70-8) → (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
With morpholine; 1,3,5-trichloro-2,4,6-triazine In water at 20℃; for 0.5h;	98%
Stage #1: 2-[4-(2'-methoxyethyl)phenoxymethyl]oxirane With β‐cyclodextrin In water; acetone at 60℃; Stage #2: With thionyl chloride In water; acetone at 20℃; for 10h;	91%
With zirconyl chloride In acetonitrile at 20℃; for 1.16667h;	80%
With water; acetyl chloride In dichloromethane for 12h;

4-(2-methoxyethyl)phenol (56718-71-9) + epichlorohydrin (106-89-8) → 2-[4-(2'-methoxyethyl)phenoxymethyl]oxirane (56718-70-8) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
With sodium hydroxide	A 90% B 10%
Stage #1: 4-(2-methoxyethyl)phenol With potassium hydroxide In methanol at 40 - 45℃; for 1h; Stage #2: epichlorohydrin at 40℃; for 24h;
With sodium hydroxide In water at 30 - 40℃; for 5h; Temperature;

4-(2-methoxyethyl)phenol (56718-71-9) → (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaOH / 12 h / 20 °C 2.1: β-cyclodextrin / H2O; acetone / 60 °C 2.2: 91 percent / thionyl chloride / H2O; acetone / 10 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 24 h / 85 °C 2: water; acetyl chloride / dichloromethane / 12 h View Scheme

2-bromo-1-(4'-hydroxyphenyl)-1-ethanone (2491-38-5) → (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol 2: H2; AcOH / Pd/C 3: 10 percent / aq. NaOH View Scheme

alpha-methoxy-4-hydroxyacetophenone (32136-81-5) → (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: H2; AcOH / Pd/C 2: 10 percent / aq. NaOH View Scheme

4-Hydroxyacetophenone (99-93-4) → (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: CuBr2 / ethyl acetate 2: methanol 3: H2; AcOH / Pd/C 4: 10 percent / aq. NaOH View Scheme

4-(2-methoxyethyl)phenol (56718-71-9) + epichlorohydrin (106-89-8) → (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
Stage #1: 4-(2-methoxyethyl)phenol With potassium hydroxide In methanol at 40 - 45℃; for 1h; Stage #2: epichlorohydrin at 40℃; for 24h; Stage #3: With acetic acid; lithium chloride In tetrahydrofuran at 20℃; for 48h;	34.88 g

4-(2-methoxyethyl)phenol (56718-71-9) + epichlorohydrin (106-89-8) → C21H28O5 + 2-[4-(2'-methoxyethyl)phenoxymethyl]oxirane (56718-70-8) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4)

Conditions	Yield
With tetrabutyl-ammonium chloride at 110℃; under 2100.21 Torr; for 0.95h; Flow reactor;

vinyl stearate (111-63-7) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → (2S)-1-chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propyl stearate (1107647-82-4)

Conditions	Yield
With Novozym 435 In hexane; acetone at 37℃; for 28h; Molecular sieve;	35.4%

vinyl acetate (108-05-4) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → Acetic acid (R)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester + Acetic acid (S)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester

Conditions	Yield
In various solvent(s) at 25℃; for 144h; native lipase B from Candida antarctica; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

vinyl acetate (108-05-4) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → Acetic acid 1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester (1017859-19-6)

Conditions	Yield
With Novozym 435 In hexane; acetone at 37℃; for 28h;

vinyl oleate (3896-58-0) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → C30H49ClO4

Conditions	Yield
With Novozym 435 In hexane; acetone at 37℃; for 28h;

vinyl laurate (2146-71-6) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → C24H39ClO4

Conditions	Yield
With Novozym 435 In hexane; acetone at 37℃; for 28h;

vinyl acetate (108-05-4) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → (S)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol + Acetic acid (R)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester

Conditions	Yield
With pseudomonas fluorescens lipase In toluene at 30℃; for 3h; Catalytic behavior; Solvent; Temperature; Resolution of racemate; Enzymatic reaction; enantioselective reaction;	A n/a B n/a

vinyl acetate (108-05-4) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → (S)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol + (R)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol + Acetic acid (R)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester + Acetic acid (S)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester

Conditions	Yield
With thermomyces lanuginosus In toluene at 30℃; Reagent/catalyst; Resolution of racemate; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a D n/a

vinyl acetate (108-05-4) + (+/-)-1-[4-(2-methoxyethyl)phenoxy]-3-chloro-2-propanol (56718-76-4) → (S)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol + Acetic acid (R)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester + Acetic acid (S)-1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester

Conditions	Yield
With Candida rugosa In toluene at 30℃; Reagent/catalyst; Resolution of racemate; Enzymatic reaction; enantioselective reaction;	A n/a B n/a C n/a

Upstream product

• 56718-71-9 4-(2-methoxyethyl)phenol 
• 106-89-8 epichlorohydrin 
• 32136-81-5 alpha-methoxy-4-hydroxyacetophenone 
• 2491-38-5 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone 
• 56718-70-8 2-[4-(2'-methoxyethyl)phenoxymethyl]oxirane 
• 99-93-4 4-Hydroxyacetophenone 

Downstream Products

• 1017859-19-6 Acetic acid 1-chloromethyl-2-[4-(2-methoxy-ethyl)-phenoxy]-ethyl ester 
• 1107647-82-4 (2S)-1-chloro-3-[4-(2-methoxyethyl)phenoxy]-2-propyl stearate 

Relevant articles and documents

Method for preparing metoprolol succinate

The invention relates to a method for preparing high-purity metoprolol succinate, which adopts a single solvent system to prepare the metoprolol succinate in a reverse dropping mode. The method is simple and convenient to operate, stable in process, high in salifying yield and purity, low in process cost, and has good practical value. A single conventional solvent is adopted, so that post-treatment and solvent recovery are facilitated, and the method is environment-friendly.

Continuous and convergent access to vicinyl amino alcohols

Five active pharmaceutical ingredients (APIs) containing the vicinyl amino alcohol moiety were synthesized using a convergent chemical assembly system. The continuous system is composed of four flow reaction modules: biphasic oxidation, Corey-Chaykovsky epoxidation, phenol alkylation, and epoxide aminolysis. Judicious choice of reagents and module order allowed for two classes of β-amino alcohols, aryl and aryloxy, to be synthesized in good (27-69%) overall yields.

Synthesis of β-chlorohydrins in water

2,4,6-Trichloro-1,3,5-triazine (TCT, cyanuric chloride) was found to mediate the regio- and stereoselective ring opening of epoxides in H 2O in the presence of morpholine at room temperature to afford the corresponding β-chlorohydrins in excellent yields (Table). The transformation is very simple, fast, efficient, and ecologically beneficial.