JPS6067451A - 2-acetyl-2-amino-ethyl alcohol and production thereof - Google Patents

Abstract

NEW MATERIAL:2-Acetyl-2-amino-ethyl alcohol expressed by formula I . USE:A synthetic intermediate for cimetidine, having the histamine H2-receptor antagonistic action, and expressed by formula II. PREPARATION:Serine is reacted with methyl lithium in an aprotic solvent, e.g. dioxane, to give the compound expressed by formula I . The reaction proceeds smoothly by using 2mol or more - a slight excess, based on 1mol serine, methyl lithium. The reaction temperature is within -30-+40 deg.C, preferably -10-+10 deg.C range, and the reaction time is usually within 8-24hr range.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 2-acetyl-2-amino-ethyl alcohol represented by the formula (I) CH3-C0\CH-CH2-OH(I)/H2 and a method for producing the same.

The compound represented by the formula (I), which is the object compound of the present invention, is particularly useful as a pharmaceutical, and has N-cyano N'-methyl-N"-( 2-[(/I-Methyl-5-imidazolyl)methylthio]ethyl)guanidine (generic name: cimetidine) According to the present invention, the compound represented by formula (I) is novel and uses a known amino acid as a starting material. It can be easily produced in one step with high yield using serine, which is a type of serine.The racemic form of serine used here is usually used from an economic point of view, but it is particularly important for optically active serine. I don't ask about it.

Examples of methods for producing the compound of formula (I>) include the following methods.

That is, it is obtained by reacting serine with methyllithium in an aprotic solvent.

This reaction proceeds quantitatively with 2 moles of methyllithium per mole of serine, but usually 2 moles of methyllithium is used.
The reaction proceeds more smoothly if a molar or more molar amount or a slightly excess molar amount is used. The reaction temperature is -30 to 40°C, preferably -1
The reaction time is usually 8 to 24 hours, depending on the reaction temperature and the type of solvent used.

Examples of the aprotic solvent used in this reaction include dioxane, dimethylbormamide, dimethyl sulfoxide, tetrahydrofuran, and ether.

Still another method is to dissolve serine in an acetic anhydride-pyridine solution, heat the solution to reflux for about 4 to 10 hours, and then add a basic substance, such as putrium hydroxide, to the reaction site. Hydrolysis can be carried out to obtain compounds of formula (I).

To separate and purify the target compound obtained by the above-mentioned production method from the reaction mixture, there is no need to use any special method, and well-known means commonly used for the purpose in the field, such as solvents, can be used. A purified product can be easily obtained by appropriately selecting and using a method such as extraction, washing, solvent distillation, crystallization, or column chroma 1 to graphie.

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 Serine (racemic form) 10.5 (+ dioxane 10
011N! A solution of ethyl ether 4olllβ in which 5.0g of methyllithium was dissolved was stirred at room temperature for 3 hours.
The mixture was added for 0 minutes, and the reaction was further allowed to occur overnight. After the reaction, 100111 J of water was poured into the reaction solution under cooling. was added. The solvent was distilled off under reduced pressure and recrystallized with ethanol to obtain 8.0 g of crystals of 2-acetyl-2-amine ethyl alcohol.

The melting point and elemental analysis values of this product are as follows.

Melting point = 3 to 248°C Elemental analysis value: as C4HEINO2 (monomer 11%) Example 2 Dimethyl sulfoxide 10 containing 10.0 g of L-serine
Ethyl ether 40111J with 4.50 methyllithium dissolved in 0ml! solution under stirring; ÷ 5°C
was added, and the reaction was continued day and night.

After the reaction, 10,011 liters of water was added, and the solvent was distilled off under reduced pressure. The residue was recrystallized with ethanol to obtain 7.8 g of crystals of 2-acetyl-2-amino-ethyl alcohol.

The melting point and elemental analysis values of this product are as follows: Melting point = 243-248°G Elemental analysis value: C4H9NO2 Example 3 40mft of pyridine and 62I111 acetic anhydride were placed in a round bottom flask equipped with a reflux device, and further L- Serine 10. ! After the reaction, the solvent was distilled off under reduced pressure, and the residue was mixed with ethanol 100+nj.
! and 4.0 g of sodium hydroxide dissolved in 50 mβ of water.
was added and heated under reflux at 75° C. for 1 hour while stirring. After adding 100,111 J of a 10% aqueous hydrochloric acid solution to this liquid and distilling off the solvent under reduced pressure, water was added and extracted three times with chloroform to remove impurities, and the aqueous layer was concentrated to dryness under reduced pressure. , 7.8 g of crystals of 2-acetyl-2-amine ethyl alcohol were obtained.

The melting point and elemental analysis values of this product are as follows.

Melting point = 243-24B'f:.

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Claims (3)

[Claims] (1) 2-acetyl-2-amino-ethyl alcohol represented by formula (I>). (2) A method for producing 2-acetyl-2-amino-ethyl alcohol represented by the formula (), which comprises reacting serine with methyllithium in an aprotic solvent. (3) Represented by the formula (I) CI-1a -C○\0H-CH2-OH(I)/H2, characterized in that serine is reacted in an acetic anhydride-pyridine solution and hydrolysis is performed after the reaction. A method for producing 2-acetyl-2-amino-ethyl alcohol.