AU2016102311A4

AU2016102311A4 - Nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method

Info

Publication number: AU2016102311A4
Application number: AU2016102311A
Authority: AU
Inventors: genan guan
Original assignee: Xiamen Kai Er Li Information Technology Co Ltd
Current assignee: Xiamen Kai Er Li Information Technology Co Ltd
Priority date: 2015-12-25
Filing date: 2016-12-24
Publication date: 2017-02-23
Anticipated expiration: 2024-12-24

Abstract

Nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method, comprising the following steps: equipped with a stiffer, a thermometer, a dropping funnel, the reaction vessel was added 1.3mol 1-amino-2-ethoxy-naphthalene(2) solution, 1.5-1.8mol 1-hydroxy-1-methyl-formamide(3) solution, 500ml cyclohexane solution, 0.6mol alumina, controlling the stirring speed at 110-160rpm, the solution temperature was raised to 60-67 C , reacted for 5-7h, the solution temperature was increased to 80-85 C, the reaction was continued for 110-130min, reducing the solution temperature to 10-15 'C , 300ml potassium bromide solution was added, standing for 30-35h, the precipitated solid was suction filtered, washed with salt solution, washed with ethyl acetate solution, washed with acetonitrile solution, dehydrated with dehydrating agent, recrystallized from ethylamine solution, got crystals of 2-ethoxy-1-naphthaldehyde.

Description

Nafcillin sodium drug intermediates 2-ethoxy-l-naphthaldehyde synthesis method

TECHNICAL FIELD

The present invention relates to nafcillin sodium drug intermediates 2-ethoxy-l-naphthaldehyde synthesis method.

BACKGROUND ART

Nafcillin sodium has similar effects with oxacillin, is characterized by acid, penicillinase-resistant, it can suck the mouth, but also the injection, mainly for respiratory tract infections caused by MRSA skin infections, it can also be used for osteomyelitis. The semi-synthetic penicillin strains characterized by acid-resistant and enzyme-resistant, acid stability, and penicillin enzyme stability, it may be administered orally, parenterally as well. The product have good effects on the staphylococcus aureus that produces penicillinase or resistant to penicillin-G, it have good effects on hemolytic streptococcus, viridans streptococcus, it also have significant bactericidal effect on pneumococcus and other gram-positive bacteria. 2-Ethoxy-1-naphthaldehyde as nafcillin sodium drug intermediates, its synthesis method is of great economic significance for improving drug synthesis product quality, reducing the by-product content.

SUMMARY OF THE INVENTION

Object of the present invention is to provide nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method, comprising the following steps: (i) equipped with a stirrer, a thermometer, a dropping funnel, the reaction vessel was added 1.3mol l-amino-2-ethoxy-naphthalene(2) solution, 1.5-1.8mol 1 -hydroxy- l-methyl-formamide(3) solution, 500ml cyclohexane solution, 0.6mol alumina, controlling the stirring speed at 110-160rpm, the solution temperature was raised to 60-67 °C, reacted for 5-7h, the solution temperature was increased to 80-85 °C, the reaction was continued for 110-130min, reducing the solution temperature to 10-15°C, 300ml potassium bromide solution was added, standing for 30-35h, the precipitated solid was suction filtered, washed with salt solution, washed with ethyl acetate solution, washed with acetonitrile solution, dehydrated with dehydrating agent, recrystallized from ethylamine solution, got crystals of 2-ethoxy-1-naphthaldehyde (1); wherein, the l-amino-2-ethoxy-naphthalene solution in step(i) has a mass fraction of 70-75%, the 1 -hydroxy- 1-methyl-formamide solution in step(i) has a mass fraction of 60 -65%, the cyclohexane solution in step(i) has a mass fraction of 30-35%, the potassium bromide solution in step(i) has a mass fraction of 25-30%, the salt solution in the step(i) is any one of ammonium bromide or potassium nitrate, the ethyl acetate solution in step(i) has a mass fraction of 65-70%, the acetonitrile solution in step(i) has a mass fraction of 75-80%, the dehydrating agent in step(i) is any one of phosphorus pentoxide, solid potassium hydroxide, the triethylamine solution in step(i) has a mass fraction of 95-98%.

Throughout the reaction can be summarized as the following reaction formula:

Advantage of the present invention is that: reducing the reaction intermediate links, decreasing the reaction temperature and reaction time, improving the reaction yield.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

Embodiment 1

Equipped with a stirrer, a thermometer, a dropping funnel, the reaction vessel was added 1.3mol l-amino-2-ethoxy-naphthalene(2) solution with a mass fraction of 70%, 1.5mol 1 -hydroxy- l-methyl-formamide(3) solution with a mass fraction of 60%, 500ml cyclohexane solution with a mass fraction of 30%, 0.6mol alumina, controlling the stirring speed at llOrpm, the solution temperature was raised to 60 °C, reacted for 5h, the solution temperature was increased to 80 °C, the reaction was continued for llOmin, reducing the solution temperature to 10 °C, 300ml potassium bromide solution with a mass fraction of 25% was added, standing for 30h, the precipitated solid was suction filtered, washed with ammonium bromide solution, washed with ethyl acetate solution with a mass fraction of 65%, washed with acetonitrile solution with a mass fraction of 75%, dehydrated with phosphorus pentoxide, recrystallized from ethylamine solution with a mass fraction of 95%, got crystals of 2-ethoxy-1-naphthaldehyde (1) 215.8g, yield 83%.

Embodiment 2

Equipped with a stirrer, a thermometer, a dropping funnel, the reaction vessel was added 1.3mol l-amino-2-ethoxy-naphthalene(2) solution with a mass fraction of 72%, 1.7mol 1 -hydroxy- l-methyl-formamide(3) solution with a mass fraction of 63%, 500ml cyclohexane solution with a mass fraction of 32%, 0.6mol alumina, controlling the stirring speed at 140rpm, the solution temperature was raised to 63 °C, reacted for 6h, the solution temperature was increased to 82 °C, the reaction was continued for 120min, reducing the solution temperature to 12°C, 300ml potassium bromide solution with a mass fraction of 27% was added, standing for 32h, the precipitated solid was suction filtered, washed with potassium nitrate solution, washed with ethyl acetate solution with a mass fraction of 67%, washed with acetonitrile solution with a mass fraction of 78%, dehydrated with solid potassium hydroxide, recrystallized from ethylamine solution with a mass fraction of 96%, got crystals of 2-ethoxy-1-naphthaldehyde (1) 22lg, yield 85%.

Embodiment 3

Equipped with a stirrer, a thermometer, a dropping funnel, the reaction vessel was added 1.3mol l-amino-2-ethoxy-naphthalene(2) solution with a mass fraction of 75%, 1.8mol 1 -hydroxy- l-methyl-formamide(3) solution with a mass fraction of 65%, 500ml cyclohexane solution with a mass fraction of 35%, 0.6mol alumina, controlling the stirring speed at 160rpm, the solution temperature was raised to 67 °C, reacted for 7h, the solution temperature was increased to 85 °C, the reaction was continued for 130min, reducing the solution temperature to 15°C, 300ml potassium bromide solution with a mass fraction of 30% was added, standing for 35h, the precipitated solid was suction filtered, washed with ammonium bromide solution, washed with ethyl acetate solution with a mass fraction of 70%, washed with acetonitrile solution with a mass fraction of 80%, dehydrated with phosphorus pentoxide, recrystallized from ethylamine solution with a mass fraction of 98%, got crystals of 2-ethoxy-1-naphthaldehyde (1) 236.6g, yield 91%.

While a number of preferred embodiments have been described, it will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

CLAIMS l.Nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method, comprising the following steps: (i)equipped with a stirrer, a thermometer, a dropping funnel, the reaction vessel was added 1.3mol l-amino-2-ethoxy-naphthalene(2) solution, 1.5-1.8mol 1-hydroxy-1-me thyl-formamide (3) solution, 500ml cyclohexane solution, 0.6mol alumina, controlling the stirring speed at 110-160rpm, the solution temperature was raised to 60-67 °C, reacted for 5-7h, the solution temperature was increased to 80-85 °C, the reaction was continued for 110-130min, reducing the solution temperature to 10-15 °C, 300ml potassium bromide solution was added, standing for 30-35h, the precipitated solid was suction filtered, washed with salt solution, washed with ethyl acetate solution, washed with acetonitrile solution, dehydrated with dehydrating agent, recrystallized from ethylamine solution, got crystals of 2-ethoxy-1-naphthaldehyde (1); wherein, the l-amino-2-ethoxy-naphthalene solution in step(i) has a mass fraction of 70-75%, the 1-hydroxy-1-methyl-formamide solution in step(i) has a mass fraction of 60 -65%, the cyclohexane solution in step(i) has a mass fraction of 30-35%, the potassium bromide solution in step(i) has a mass fraction of 25-30%, the salt solution in the step(i) is any one of ammonium bromide or potassium nitrate, the ethyl acetate solution in step(i) has a mass fraction of 65-70%.
2. Nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method according to claim 1 wherein the acetonitrile solution in step(i) has a mass fraction of 75-80%.
3. Nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method according to claim 1 wherein the dehydrating agent in step(i) is any one of phosphorus pentoxide, solid potassium hydroxide.
4. Nafcillin sodium drug intermediates 2-ethoxy-1-naphthaldehyde synthesis method according to claim 1 wherein the triethylamine solution in step(i) has a mass fraction of 95-98%.