Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of preparation method of boc-l-asparagine

A technology of asparagine and asparagine, applied in the field of medicinal chemistry, can solve the problems of unfavorable industrialization, cost, environmental protection, high safety, cumbersome operation, etc., and achieve the effect of facilitating industrial production, high safety factor, and simple operation

Active Publication Date: 2018-03-02
宜兴市前成生物有限公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the method has mild reaction conditions and a short time, and can obtain higher yields, triethylamine has a strong ammonia smell, and due to the use of an organic solvent-water solvent system, the follow-up operations are cumbersome, and after the reaction needs to be Evaporation of organic solvents, followed by extraction, water layer acid adjustment, extraction, and crystallization is not conducive to industrialization, and the cost, environmental protection, and safety requirements are also extremely high

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
  • A kind of preparation method of boc-l-asparagine
  • A kind of preparation method of boc-l-asparagine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Prepare BOC-L-asparagine according to the following preparation steps:

[0026] Step (1), 150g L-Asn (1mol), 240g di-tert-butyl dicarbonate (1.1mol) and 700mL water are put into the 3L flask; , add dropwise the NaOH aqueous solution (3mol) of 300mL10mol / L while stirring, control the rate of addition, make pH=9~10, in this process L-Asn and di-tert-butyl dicarbonate are dissolved in water and react; Afterwards, the temperature was raised to 34° C., and then reacted for 4 hours under stirring;

[0027] Step (2), the reaction solution is cooled to less than 10°C with ice-brine; slowly add 6mol / L hydrochloric acid dropwise, keep the temperature below 10°C during the dropwise addition, acidify to pH 4.3, and precipitate BOC-L-asparagine crude product, Suction filtration, wash the solid with 150 mL of water, and dry the solid at 56°C to obtain 192 g of fine BOC-L-asparagine, with a weight yield of 128% (relative to L-asparagine), and a molar yield of 90.5%.

Embodiment 2

[0029] Prepare BOC-L-asparagine according to the following preparation steps:

[0030] Step (1), 150g L-Asn (1mol), 262g di-tert-butyl dicarbonate (1.2mol) and 700mL water are put into the 3L flask; , add dropwise the NaOH aqueous solution (3mol) of 300mL10mol / L while stirring, control the rate of addition, make pH=9~10, in this process L-Asn and di-tert-butyl dicarbonate are dissolved in water and react; Afterwards, the temperature was raised to 34° C., and then reacted for 4 hours under stirring;

[0031] Step (2), the reaction solution was cooled to less than 10°C with ice-salt water, and residual (Boc) was detected 2 O crystals; slowly add 6mol / L hydrochloric acid dropwise, keep the temperature below 10°C during the dropwise addition, acidify to pH 4.3, precipitate BOC-L-asparagine crude product, filter with suction, wash the solid with 110mL water, and dry the solid at 58°C After drying, 217.5 g of BOC-L-asparagine fine product was obtained, with a weight yield of 145% ...

Embodiment 3

[0033] Prepare BOC-L-asparagine according to the following preparation steps:

[0034] Step (1), 150g L-Asn (1mol), 218g di-tert-butyl dicarbonate (1mol) and 700mL water are put into a 3L flask; at a temperature of 25 to 30°C, while maintaining a rotational speed of 120 rpm, Add dropwise 300mL of 10mol / L NaOH aqueous solution (3mol) while stirring, and control the drop rate so that pH=9~10. During this process, L-Asn and di-tert-butyl dicarbonate are dissolved in water to react; the dropwise addition is completed Afterwards, the temperature was raised to 34° C., and then reacted for 4 hours under stirring;

[0035] Step (2), the reaction solution was cooled to less than 10°C with ice-salt water, and residual (Boc) was detected 2 O crystals; slowly add 6mol / L hydrochloric acid dropwise, keep the temperature below 10°C during the dropwise addition, acidify to pH 4.3, precipitate crude BOC-L-asparagine, filter with suction, wash the solid with 100mL water, and dry the solid at 5...

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 preparation method of BOC-L-asparagine. The preparation method comprises the following steps: using L-asparaginate and di-tert-butyl dicarbonate ester as raw materials and water as a reaction solvent to carry out a reaction under the alkaline condition of pH 9-10 to generate BOC-L-asparagine, acidizing a reaction liquid to pH 4.0-4.5 to precipitate out a BOC-L-asparagine crude product, carrying out suction filtration, washing with water and drying to obtain a BOC-L-asparagine refined product. The preparation method of BOC-L-asparagine has advantages of mild reaction condition, fast reaction and lower cost of raw materials. As water is used as the reaction solvent, the subsequent operation is simple, and BOC-L-asparagines crystal can be precipitated out only by acidifying. The method is beneficial to industrial production, is environment friendly and has high safety factor.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of BOC-L-asparagine. Background technique [0002] L-asparagine is used to synthesize organic raw materials or pharmaceutical intermediates. When utilizing L-asparagine to synthesize and design, it is often necessary to protect the amino group. Boc (tert-butoxycarbonyl) is a better amino group Protecting groups have been widely used in synthetic design. BOC-L-Asparagine (BOC-L-Asparagine), also known as: N-tert-butoxycarbonyl-L-Asparagine, white crystalline substance, soluble in DMF, insoluble in petroleum ether. Molecular formula: C 9 h 16 N 2 o 5 ; The structural formula is as follows: [0003] [0004] Qiu Chuanliang and others investigated the Bocization of amino dibasic acids. Iminodiacetic acid and aspartic acid were combined with (Boc) in an alkaline 1,4-dioxane-water solvent system. 2 O reaction and glutamic acid with (Boc) in ...

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 Patents(China)
IPC IPC(8): C07C269/04C07C271/22
CPCC07C269/04C07C271/22
Inventor 席日新刘涛
Owner 宜兴市前成生物有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products