JPS58113169A - Synthesis of 1-(4-isopropylthiophenyl)-2-n- octylaminopropanol, ester thereof and salt - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for synthesizing 1-(4-isopropylthiotunyl)-2-n-octylaminopropatur (suloctidyl) represented by formula I, its salts and esters.

If the derivative represented by formula (2) is in the form of an acid addition salt, it may be transformed into a free salt or another acid addition salt by a known method.

Commonly used salts are acid addition salts, especially non-toxic pharmaceutically available acids, such as suitable inorganic acids such as hydrochloric, sulfuric, and phosphoric acids, or aliphatic, cycloaliphatic, and aromatic acids. aromatic aliphatic acids, or suitable organic acids such as heterocyclic acids, carbosalic acids or sulfonic acids, such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, glyconic acid, lactic acid,
Malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, oxybenzoic acid,
salicylic acid, 7-nyl acetic acid, mandelic acid, embonic acid,
Methylsulfonic acid, ethylsulfonic acid, pantothenic acid,
These are addition salts of toluenesulfonic acid, sulfanilic acid, cyclohexylaminosulfonic acid, glucuronic acid, etc.

Commonly used esters include acetic acid, propionic acid, cyclopentanecarboxylic acid, cyclopentanecarboxylic acid, hinocrine, methylthiobutylacetic acid, cyclohexaneacetic acid, alkoxyphenylacetic acid, and 2-methylpropionic acid.

When the method of the present invention produces a novel intermediate compound, this novel compound also contributes to its production, i.e., according to the following formula, 1-(4-thiophenyl) represented by the formula
-2-n-octylaminopropanol is inert due to the presence of 1θ〇-0, H, X (in the formula, X represents an easily separable group) and a basic auxiliary agent. Alkylation is carried out by reaction in a solvent or water.

H3 V VI ■ In the formula (■), X represents a group that readily undergoes a substitution reaction, such as a tosyl group or mesyl group, or a halogen such as chlorine, bromine, or iodine. It is preferable to introduce an organic or inorganic base into the reaction mixture. As the base, sodium hydroxide or potassium hydroxide, triethylamine, pyridine, 1JN-dimethylaniline, etc. can be used. It also proceeds in the presence of a phase transfer catalyst, such as tetra-n-butylammonium hydroxide.

Depending on the reagents involved, the reaction is carried out at a temperature between ambient temperature and the reflux temperature of the solvent used.

Alternatively, as a modification of this method, 1-(4-thiotunyl)-2-n-octylaminopropanol of formula V and propene of formula (2) can be reacted in a strong acid medium according to the following formula.

■ ■ ■ Generally, an excess amount of olefin and a strong acid, for example 75%4
A acid or concentrated hydrochloric acid, nitric acid or phosphoric acid is applied, and then the mixture is heated at -20°C to 50°C, preferably 0°C while stirring.
Add the entire thiophenolic acid derivative at a temperature close to . The temperature of the reaction mixture is then returned to room temperature, and the p-product is separated by a method known in the field of organic chemistry.

Thiotunol ■ is diazotized to the corresponding 1-amino acid,
The diazonium base is obtained, for example, by treatment with hydrogen sulfide.

Example 1 11.8 g of 1-(4-thiophenyl)-2-n-octylaminopropatol and inglobilt silane) 14
．． 7 g (0.05 mol) total 15% sodium hydroxide aqueous solution 25 mt (/C bath power) and heated to 75° C. for 2 hours with stirring.

After cooling, add 50 yd' of water and filter. -20℃ n
- Recrystallize in hebutane and filter. If necessary, n
- Recrystallize in hebutane or acetone.

Melting point: 61. -64℃.

Example 2 Inpropatool 50 1-(4-thiotunyl)-
2-octylaminopropatool 14.7g (0.05
mol) and 2.2 g of sodium hydroxide, the mixture was heated to 60°C, and then 7.38 g of isopropyl bromide was added.
g (0.06 mol). Evaporate to dryness and recover the residue with 30 ml of total water and 50 ml of toluene. After complete dissolution, the organic phase is separated, washed thoroughly, treated with animal charcoal, and filtered through Celite for 1 hour. The solvent was completely evaporated under vacuum, crystallized using n-hebutane, filtered at -20°C, and recrystallized in acetone.

Melting point: 63.4℃ patent applicant Continental Fu7-ma patent application agent Patent attorney Akira Aoki Patent Attorney Nishidate O [1] Patent attorney Tera 1) Yutaka Patent attorney Akiyuki Yamaguchi 605-

Claims (1)

[Claims] 1.1-(4-thiotunyl)-2-n-octylaminopropatol total alkylating agent, formula OH. = reacted with CH-OHs in a strongly acidic medium or with the formula iθo -0,H, 1-(4-Inglobil) is characterized in that it is reacted to exhaustion in a solvent or water, and depending on the case, it can be converted into its salt by adding an inorganic or organic acid, or converted into its ester by adding an active derivative of an organic acid. Method for producing thiofunyl)-2-n-octylaminopropanol, its salts and esters.