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

A kind of improved synthetic method of α-amino-γ-butyrolactone hydrochloride

A synthesis method and butyrolactone technology, applied in the direction of organic chemistry and the like, can solve the problems of difficult environmental protection treatment, long reaction time, high price, etc., and achieve the effects of low environmental protection treatment difficulty, simple operation and easy control, and reduced production cost.

Inactive Publication Date: 2018-06-05
HUBEI UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] 1. Synthetic method of methyl iodide, which is to use L-methionine and methyl iodide to react to generate (S)-methionine thiomethyliodonium salt, and its sulfonium salt can be used after separation and purification, or directly use the crude product for the next step step reaction, and its representative documents include Molecules, 2014,19(10):16349; Org. Lett, 2008, 10(24):5521-5524; EuropeanJ Med Chem, 2015, 93:321-329; Tetrahedron:Asymmetry, 2013, 24(11): 663-668;Synthesis, 1993, 11: 1065-1067; Tetrahedron:Asymmetry, 1995, 6(11): 2819;Chem Pharm Bull,1996, 44(12): 2322-2325; Chemical Intermediates, 2008, 38(3):21-21; Chemical Reagents, 2008, 30(2): 117-119; Pesticides 2006, 45(1), 22-23,30; CN 1680312 (2005);Chinese Chemical Letters, 2006, 17 (2), 177-179 etc., the product purity that this method synthesizes is higher, but its shortcoming is that methyl iodide is highly toxic and expensive, and the reaction time is long, and production cost is high, especially iodide ion is mixed into Difficult to separate from the product, often requiring an additional oxidative deiodination step
[0004] 2. The synthesis method of haloacetic acid. This method is to react methionine with chloro or bromoacetic acid to produce a sulfonium salt intermediate, and then replace it with a hydroxyl group under acidic conditions to produce homoserine. The representative literature is JP 2012140390 (2012); CN103282355 (2013); Microchemical Journal 1989, 4: 226-232; EP 2012093565 (2012); EP 2010068371 (2010) etc., this method has advantages such as raw material cost is low, reaction time is short compared with iodomethane synthetic method, but its existence produces The by-product MeSCH2COOH is difficult to recycle, and the disadvantages of environmental protection are difficult, and excessive chloro or bromoacetic acid may cause amino acid amino groups to undergo N-alkylation reaction by-products, affecting product purity and yield
[0005] 3. The synthesis method of dimethyl sulfate. The literature reported on this method is only CN 102321004 A (2012). The synthesis method is to react methionine with dimethyl sulfate in a molar ratio of 1.0~1.5 to produce methionine thiomethylmethsulfate intermediate body, and then direct alkali hydrolysis hydroxylation reaction and acidic esterification ring-closing reaction to synthesize the target α-amino-γ-butyrolactone hydrochloride, but unfortunately the literature does not report the yield, which has short reaction time and raw materials The advantages of low cost and low difficulty in wastewater treatment, but the disadvantages are also very obvious. It requires the use of dimethyl sulfate with a molar ratio of methionine of 1.0 to 1.5, which not only increases the amount of methylation reagents and increases production costs, but also excess formazan Methylation ability may carry out N-methylation reaction on the amino group of amino acid, affecting product purity and yield

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Add 10mL H in the 50mL flask of embodiment one 2 O, 2 mL of ethanol and 3.0 g (0.02 mol) of L-methionine, then slowly add 1.0 g (0.01 mol) of concentrated H under stirring 2 SO 4 , after the suspended solid is dissolved, add 1.26 g (0.01mol) dimethyl sulfate, react at room temperature for 4 h, then add 1.10 g (0.008mol) dimethyl sulfate, heat up to 40 0 C continues to react for 4h, after TCL detects that the conversion of methionine is completed, the solvent alcohol is recovered by distillation under normal pressure, then cooled to room temperature and then added with Na 2 CO 3 Adjust the pH of the reaction solution to 8~9 with a saturated aqueous solution, then raise the temperature to 40°C and continue the reaction for 10 h. Evaporate most of the aqueous solution under reduced pressure, add 10 mL of 6 mol / L hydrochloric acid solution, heat to reflux for 2.0 h, and then remove the solvent under reduced pressure. Evaporate to dryness to obtain a solid or viscous prod...

Embodiment 2

[0019] Example 2 Add 10mL H to a 50mL flask 2 O, 2 mL methanol and 3.0 g (0.02 mol) L-methionine, then add 1.76 g (0.014 mol) dimethyl sulfate, stir at room temperature for 2 h, after the suspended solid dissolves, slowly add 2.0 g (0.02 mol) concentrated H 2 SO 4, after raising the temperature to 40°C and continuing the reaction for 6 h, the solvent methanol was recovered by raising the temperature, and then NaHCO was added in small amounts under rapid stirring. 3 Solid powder, adjust the pH of the reaction solution to about 8~9, continue to react at 40°C for 10 h, evaporate most of the aqueous solution under reduced pressure, add 8 mL of 6 mol / L hydrochloric acid solution, heat to reflux for 2 h, and then evaporate the solvent to dryness under reduced pressure , to obtain a solid or viscous product, the product was extracted with hot methanol, and the crude product was processed by conventional recrystallization to obtain 2.1 g of α-amino-γ-butyrolactone hydrochloride, with...

Embodiment 3

[0020] Example 3 Add 6mL of H to a 50mL flask 2 O, 6mL methanol and 3.0 g (0.02mol) D-methionine, then slowly add 2.4g (0.024mol) concentrated H 2 SO 4 After the suspended solid dissolves rapidly, slowly add 2.02g (0.016mol) dimethyl sulfate dropwise at room temperature, and then raise the temperature to 40 0 C stirs the reaction for 6 h, heats up to reclaim the solvent methanol, and then adds K 2 CO 3 Adjust the pH to 9~10 with saturated aqueous solution, continue to react overnight at 40°C, evaporate the solvent to almost dryness under reduced pressure, add 50mL methanol to the residue and reflux for 30min, filter out the salt while hot, spin the filtrate dry, and add 8 mL of 6 mol / L hydrochloric acid solution, heated to reflux for 3.0 h, and then evaporated the solvent to dryness under reduced pressure to obtain a solid or viscous product. The product was extracted with hot methanol, and the crude product was processed by conventional recrystallization to obtain α-amino-...

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 provides an improved method for synthesizing alpha-amino-gamma-butyrolactone hydrochloride by using methionine and dimethyl sulfate as raw materials. The method has the following key steps: reacting methionine with dimethyl sulfate to generate a sulfonium salt in the presence of sulfuric acid as an accelerant, and then performing hydroxylation and acidic closed-ring reaction to synthesize a target substance. The reactions of three steps are finished by virtue of a one-pot method, and the total yield can reach 83%.

Description

technical field [0001] The invention relates to the field of synthesis of pharmaceutical intermediates, in particular to an improved method for synthesizing alpha-amino-gamma-butyrolactone hydrochloride using methionine, dimethyl sulfate and sulfuric acid as starting materials. Background technique [0002] α-Amino-γ-butyrolactone hydrochloride is an important intermediate in the synthesis of chiral herbicide pesticide glufosinate, and it can also be used in chiral drugs such as canavanine, paracanavanine, selenomethionine and The synthesis of adenosylmethionine, etc., in addition, it can also be used in the synthesis of bacterial sensing signal molecular probes, and it is a drug intermediate with a wide range of applications. The synthesis of chiral α-amino-γ-butyrolactone hydrochloride is usually synthesized from natural methionine through a three-step process of sulfonium salt reaction, desulfurization methyl hydroxylation reaction and acidic esterification ring closure r...

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): C07D307/33
CPCC07D307/33
Inventor 李焰
Owner HUBEI UNIV