Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for synthesizing tert-butyl acetylene which is intermediate of terbinafine medicines

A technology of terbinafine and synthesis method, which is applied in the field of synthesis of terbinafine pharmaceutical intermediate tert-butylacetylene, can solve the problems such as the reduction of terbinafine clearance rate, achieve reduction of reaction temperature and reaction time, increase Reaction yield, the effect of reducing intermediate links

Inactive Publication Date: 2017-01-04
XIAMEN KAI ER LI INFORMATION TECH CO LTD
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In patients with hepatic disease, a single-dose pharmacokinetic study showed that the clearance of terbinafine was reduced by approximately 50%

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing tert-butyl acetylene which is intermediate of terbinafine medicines

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0012] In the reaction vessel that stirrer, thermometer, dropping funnel, condenser are installed, add mass fraction and be 30% potassium bisulfite solution 310ml, mass fraction is 60% hexane 300ml, raise solution temperature to 90 ℃, control Stir at 150rpm, add 0.73mol of 1,1-diamino-3,3-dimethylbutane (2) dropwise, control the dropwise addition time at 3h, add 0.81mol of phenyl hypochlorite (3), and react for 90min , raise the temperature of the solution to 110°C, continue the reaction for 3h, lower the temperature of the solution to 10°C, precipitate solids, filter, wash with potassium iodide solution, wash with acetonitrile with a mass fraction of 80%, distill under reduced pressure at 1.1kPa, collect 100--108°C Fractions were recrystallized in 90% cyclohexane to obtain 41.30 g of crystalline tert-butylacetylene with a yield of 69%.

example 2

[0014] In the reaction vessel that stirrer, thermometer, dropping funnel, condenser are installed, add mass fraction and be 32% potassium bisulfite solution 310ml, mass fraction is 62% hexane 300ml, raise solution temperature to 92 ℃, control Stir at 160rpm, add 0.73mol of 1,1-diamino-3,3-dimethylbutane (2) dropwise, control the dropwise addition time at 4h, add 0.83mol of phenyl hypochlorite (3), and react for 110min , raise the solution temperature to 112°C, continue the reaction for 4h, lower the solution temperature to 12°C, precipitate solids, filter, wash with ammonium chloride solution, wash with acetonitrile with a mass fraction of 82%, distill under reduced pressure at 1.2kPa, collect 100--108 The fraction at ℃ was recrystallized in cyclohexane with a mass fraction of 92% to obtain 43.09 g of crystalline tert-butylacetylene, with a yield of 72%.

example 3

[0016] In the reaction vessel that stirrer, thermometer, dropping funnel, condenser are installed, add mass fraction and be 35% potassium bisulfite solution 310ml, mass fraction is 65% hexane 300ml, raise solution temperature to 95 ℃, control Stirring speed is 170rpm, 0.73mol of 1,1-diamino-3,3-dimethylbutane (2) is added dropwise, the dropping time is controlled at 5h, 0.84mol of phenyl hypochlorite (3) is added, and the reaction is 120min , raise the temperature of the solution to 115°C, continue the reaction for 5h, lower the temperature of the solution to 15°C, precipitate a solid, filter, wash with potassium iodide solution, wash with acetonitrile with a mass fraction of 85%, distill under reduced pressure, collect the fraction at 100--108°C, Recrystallized in 1.3 kPa cyclohexane to obtain 47.29 g of crystalline tert-butylacetylene with a yield of 79%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for synthesizing tert-butyl acetylene which is an intermediate of terbinafine medicines. The method includes steps of adding 310 ml of potassium bisulfite solution and 300 ml of hexane into reaction vessels with stirrers, thermometers, dropping funnels and condensers to obtain solution, increasing the temperature of the solution until the temperature of the solution reaches 90-95 DEG C and stirring the solution at the stirring speed of 150-170 rpm under the control; dropwise adding 0.73 mol of 1, 1-diamino-3, 3-dimethyl butane into the solution for the dropwise adding time of 3-5 h under the control; adding 0.81-0.84 mol of hypochlorous acid phenyl ester into the solution; carrying out reaction for 90-120 min; increasing the temperature of solution until the temperature of the solution reaches 110-115 DEG C; continuing to carry out reaction for 3-5 h; reducing the temperature of the solution until the temperature of the solution reaches 10-15 DEG C; precipitating solid; filtering the solid; washing the solid by the aid of salt solution; washing the solid by the aid of acetonitrile; carrying out reduced-pressure distillation; collecting distillate at the temperature of 100-108 DEG C; re-crystallizing the distillate in cyclohexane to obtain the tert-butyl acetylene which is a crystal.

Description

technical field [0001] The invention relates to a method for synthesizing terbinafine drug intermediate tert-butylacetylene. Background technique [0002] Terbinafine is an allylamine drug that is effective against pathogenic fungi of the skin, hair and nails including dermatophytes such as Trichophyton (such as Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verruca, Trichophyton trichophyton, Trichophyton violaceum), Microsporum (e.g. Microsporum canis), Epidermophyton flocculus, and yeasts of the genera Candida (e.g. Candida albicans) and Pityrosporum are broadly resistant to fungal activity. For yeast, it has a bactericidal effect or a bacteriostatic effect depending on the strain. Terbinafine specifically interferes with the early steps of fungal sterol biosynthesis, thereby causing ergosterol deficiency and intracellular accumulation of squalene, leading to fungal cell death. Terbinafine works by inhibiting squalene epoxidase on the fungal cell membra...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C1/00C07C11/22
CPCC07C1/00C07C11/22
Inventor 关艮安
Owner XIAMEN KAI ER LI INFORMATION TECH CO LTD