469-21-6

Basic information

• Product Name: DOXYLAMINE
• Synonyms: N,N-Dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]ethanamine;NCI C60684;Phenyl-2-pyridylmethyl-beta-N,N-dimethylaminoethyl ether;Pyridine, 2-[alpha-[2-(dimethylamino)ethoxy]-alpha-methylbenzyl]-;DOXYLAMINE;dimethyl(2-(1-phenyl-1-(2-pyridyl)ethoxy)ethyl)amine;2-[a-(2-dimethylaminoethoxy)-a-methylbenzyl]pyridine;2-dimethylaminoethoxyphenylmethyl-2-picoline
• CAS NO: 469-21-6
• Molecular Formula: C₁₇H₂₂N₂O
• Molecular Weight: 270.37
• EINECS: 207-414-2
• Mol File: 469-21-6.mol

Chemical Properties

• Melting Point: 25°C
• Boiling Point: bp0.5 137-141°
• Flash Point: 174.5 °C
• Appearance: /
• Density: 1.0023 (rough estimate)
• Refractive Index: 1.5486 (estimate)
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility: Acetonitrile (Slightly), Chloroform (Slightly), Methanol (Slightly)
• PKA: pKa 9.20(H2O t = 25 c = 0.002–0.01) (Uncertain);4.4 (Uncertain);9.2 (Uncertain)
• Stability: Temperature Sensitive
• CAS DataBase Reference: DOXYLAMINE(CAS DataBase Reference)
• NIST Chemistry Reference: DOXYLAMINE(469-21-6)
• EPA Substance Registry System: DOXYLAMINE(469-21-6)

Safety Data

• Hazardous Substances Data: 469-21-6(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 469-21-6 differently. You can refer to the following data:
1. Antihistaminic.
2. (±)-Doxylamine is an intermediate in the synthesis of Doxylamine N, N’-Dioxide (D562025), which is an impurity of Doxylamine (succinate salt, D562000), which is an H1 Histamine receptor antagonist.

Brand name

Decapryn (Sanofi Aventis); Unisom (Pfizer).

General Description

Clear colorless liquid.

Reactivity Profile

DOXYLAMINE is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides

InChI:InChI=1S/C17H22N2O/c1-17(20-14-13-19(2)3,15-9-5-4-6-10-15)16-11-7-8-12-18-16/h4-12H,13-14H2,1-3H3

Upstream product

• 107-99-3 2-(dimethylamino)ethyl chloride 
• 4584-46-7 (2-chloroethyl)dimethylamine hydrochloride 
• 19490-92-7 1-phenyl-1-(pyridin-2-yl)ethanol 
• 591-50-4 iodobenzene 
• 1122-62-9 2-acetylpyridine 
• 14159-54-7 2-(1-phenylethyl)pyridine 

Downstream Products

• 15260-65-8 2-(1-phenylvinyl)pyridine 
• 19490-92-7 1-phenyl-1-(pyridin-2-yl)ethanol 
• 145823-16-1 ((2R,3R,4S,5S,6S)-6-Carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-dimethyl-[2-(1-phenyl-1-pyridin-2-yl-ethoxy)-ethyl]-ammonium; chloride 
• 562-10-7 doxylamine succinate 

Relevant articles and documents

Transition-Metal Free Chemoselective Hydroxylation and Hydroxylation-Deuteration of Heterobenzylic Methylenes

We developed an approach for direct selective hydroxylation of heterobenzylic methylenes to secondary alcohols avoiding overoxidation to ketones by using a KOBu-t/DMSO/air system. Most reactions could reach completion in several minutes to give hydroxylated products in 41-76% yields. Using DMSO-d6, this protocol resulted in difunctionalization of heterobenzylic methylenes to afford α-deuterated secondary alcohols (>93% incorporation). By employing this method, active pharmaceutical ingredients carbinoxamine and doxylamine were synthesized in two steps in moderate yields.

Synthesis method of doxylamine succinate

The invention discloses a synthesis method of doxylamine succinate. The method includes: (1) adding 2-pyridylphenylmethylcarbinol into an organic solvent I, adding a catalyst, strong base or alkali metal and 2-dimethylaminochloroethane respectively, performing heating to 100-110DEG C and carrying out reaction for 1-2h; then conducting cooling and filtering; subjecting an aqueous phase to backwashing with the organic solvent I, then performing heating to 70-80DEG C, adding activated carbon for decolorization, then performing filtering, then adding a low-boiling-point organic solvent for extraction, drying the extracted organic phase, and finally conducting reduced pressure concentration at 50-60DEG C to dryness to obtain doxylamine; and (2) dissolving the doxylamine in an organic solvent II, adding succinic acid at 50-60DEG C for reaction, then employing medicinal activated carbon for decolorization and filtering, conducting cooling to a temperature at or below 5DEG C, carrying out stirring crystallization, then performing pumping filtering, and conducting washing with the precooled organic solvent II, and finally performing vacuum drying to obtain the doxylamine succinate. The synthesis method provided by the invention simplifies operation, lowers energy consumption, and has high reaction conversion rate and high yield.

A method for preparing many west pulls sensitively succinic acid

The invention relates to a preparation method of doxylamine succinate. The preparation method comprises the steps as follows: firstly, a Grignard reagent generated by iodobenzene and magnesium reacts with 2-acetylpyridine to generate 2-pyridyl phenyl methyl alcohol, the 2-pyridyl phenyl methyl alcohol is recrystallized to be purified, then the 2-pyridyl phenyl methyl alcohol reacts with sodium amide and 2-dimethylamino chloroethane sequentially, doxylamine is obtained and has a salt forming reaction with succinic acid finally, and the doxylamine succinate is obtained. The preparation method is high in reaction efficiency, lower in cost and applicable to industrial mass production.

Preparation method of doxylamine succinate

The invention discloses a preparation method of doxylamine succinate. The preparation method comprises following steps: step 1, 2-pyridyl phenyl methyl carbinol is dissolved in an organic solvent, and is reacted with 2-dimethylaminoethyl chloride hydrochloride at high temperature, after reaction, target product N,N-dimethyl-2-[1-phenyl-1-(2-pyridine)oxethyl]ethylamine is obtained via quenching extracting separation; and step 2, N,N-dimethyl-2-[1-phenyl-1-(2-pyridine) oxethyl]ethylamine obtained in the step 1 and succinic acid are subjected to salt forming in an organic solvent; and finished product N,N-dimethyl-2-(1-phenyl-1-(2-pyridine)ethoxy)ethanamine succinate (doxylamine succinate) is obtained via cooling crystallization. The preparation method is simple, safe, and reliable, is high in doxylamine succinate yield, and is suitable for industrialized enlarged production; and post-treatment is simple and convenient.