CN104788320A

CN104788320A - Preparation method of 1,3-dimethylbutylamine hydrochloride

Info

Publication number: CN104788320A
Application number: CN201410028124.0A
Authority: CN
Inventors: 张卫军; 张新; 谈蕙芳
Original assignee: SHANGHAI XUXIN CHEMICAL Co Ltd
Current assignee: SHANGHAI XUXIN CHEMICAL Co Ltd
Priority date: 2014-01-22
Filing date: 2014-01-22
Publication date: 2015-07-22

Abstract

The invention provides a preparation method of 1,3-dimethylbutylamine hydrochloride. The preparation method comprises following steps: 1) methyl isobutyl ketone, formamide, and ammonium formate are mixed, and an obtained mixture is reacted for 19 to 21h at 120 to 170 DEG C; 2) after reaction, impurities are removed so as to obtain an intermediate product a; and 3) the intermediate product a is mixed and reacted with concentrated hydrochloric acid, and 1,3-dimethylbutylamine hydrochloride is obtained after 7 to 9h of heating reflux reaction. Operation of the preparation method is simple; reaction is mild; and preparation of 1,3-dimethylbutylamine hydrochloride with high efficiency can be realized.

Description

The preparation method of 1,3-dimethyl butyrate amine hydrochlorate

Technical field

The invention belongs to the synthetic method of compound, especially relate to the preparation method of 1,3-dimethyl butyrate amine hydrochlorate.

Background technology

1,3-dimethylamylamine hydrochloride is widely used in fat-reducing class healthcare products, because of 1,3-dimethylamylamine hydrochloride fat-reducing effect is remarkable, market demand grows with each passing day, and the side-effect problem brought also appears in one's mind gradually, and existing American-European health-product market forbids 1, the circulation of 3-dimethylamylamine hydrochloride, but in the substitute of growing slimming health product market in urgent need 1,3-dimethylamylamine hydrochloride, wherein, 1,3-dimethyl butyrate amine hydrochlorate is as the substitute products of the best; But, at present both at home and abroad also not to the description of 1,3-dimethyl butylamine hydrochloride process and synthetic method.

Summary of the invention

The object of the invention is to provide a kind of 1,3-dimethylamylamine hydrochloride preparation method.

Technical scheme of the present invention is as follows:

The preparation method of 1,3-dimethyl butyrate amine hydrochlorate, comprises the steps:

1) hexone, methane amide and ammonium formiate mixing, reacts 19-21 hour at temperature is 120-170 DEG C;

2), after reaction terminates, remove impurity, obtain middle product a;

3) step 2) in the middle product a of gained and concentrated hydrochloric acid hybrid reaction, heating reflux reaction 7-9 hour, obtains 1,3-dimethyl butyrate amine hydrochlorate.

Preferably, described step 2) in, after reaction terminates, be cooled to 35-45 DEG C, carry out water extraction, remove water layer, obtain middle product a.

Preferably, also comprise the steps:

4) 1, the 3-dimethyl butyrate amine hydrochlorate that prepared by described step 3) concentrates evaporate to dryness, obtains solid product b;

5) aqueous solution of obtained described solid product b, adds gac, 70-80 DEG C of insulation 30-40 minute;

6) filter, filtrate evaporate to dryness concentrates, and obtains product c.

Further preferably, also comprise the steps:

7) in step 6), products therefrom c adds ethyl acetate, at-2 DEG C ~ 2 DEG C temperature, and crystallize out, insulation 2.5-3.5 hour, filters;

8) filter cake ethyl acetate is washed, 75-85 DEG C of drying, obtains high purity 1,3-dimethyl butyrate amine hydrochlorate.

Wherein, the structural formula of described middle product a is:

Preferably, the molar ratio of described hexone, methane amide and ammonium formiate is: 0.3-0.5:1:0.5-1.

Preferably, in described step 3), the envelope-bulk to weight ratio of concentrated hydrochloric acid and described reaction product is 1:2 ~ 2:5.

Wherein said product b or c for containing impurity more, purity lower than 90% 1,3-dimethyl butyrate amine hydrochlorate.

Beneficial effect of the present invention is as follows:

1) the invention provides a kind of synthetic method of 1,3-dimethyl butyrate amine hydrochlorate, wherein, the invention provides technical scheme operation simple, reaction temperature and, 1,3-dimethyl butyrate amine hydrochlorate can be prepared efficiently.

2) by the adsorption of gac, remove reaction rear impurity, be further purified 1,3-dimethyl butyrate amine hydrochlorate.

3) ethyl acetate removes organic impurity, final 1, the 3-dimethyl butylamine hydrochloride product obtained, high purity 99.5%.

Accompanying drawing explanation

Fig. 1. the HPLC of 1,3-dimethyl butyrate amine hydrochlorate prepared by embodiment 1 detects collection of illustrative plates.

Embodiment

Below in conjunction with the accompanying drawing in the embodiment of the present invention, be clearly and completely described the technical scheme in the embodiment of the present invention, obviously, described embodiment is only the present invention's part embodiment, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.

Embodiment 11,3-dimethyl butyrate amine hydrochlorate

1) by hexone 8.3g, methane amide 9g, ammonium formiate 9g drop into heat temperature raising in reaction flask, treat interior temperature rise to 150 DEG C, react 20 hours.Question response terminates, and is cooled to 40 DEG C and adds 20ml water, layering, obtain oil reservoir 9g.

2) 9g oil reservoir and the dense HCl of 20ml are dropped into reaction flask, reflux is after 8 hours, evaporated under reduced pressure, solid adds 20ml water again and starts to stir, then add 0.3g gac, be heated to 70 DEG C-80 DEG C, be incubated 30 minutes, filter, filtrate reduced in volume is to dry, add ethyl acetate 50ml, be cooled to 0 DEG C, crystallization, be incubated 3 hours, filter, filter cake glacial acetic acid ethyl ester 5ml washs, 80 DEG C of dryings, obtain finished product 6.3g, content purity 99.1%.

Embodiment 21,3-dimethyl butyrate amine hydrochlorate

1) by hexone 6g, methane amide 9g, ammonium formiate 6.3g drop into heat temperature raising in reaction flask, treat interior temperature rise to 150 DEG C, react 20 hours.Question response terminates, and is cooled to 40 DEG C and adds 20ml water, layering, obtain oil reservoir 9g.

2) 9g oil reservoir and the dense HCl of 44ml are dropped into reaction flask, reflux is after 8 hours, evaporated under reduced pressure, solid adds 20ml water again and starts to stir, then add 0.3g gac, be heated to 70 DEG C-80 DEG C, be incubated 30 minutes, filter, filtrate reduced in volume is to dry, add ethyl acetate 50ml, be cooled to 0 DEG C, crystallization, be incubated 3 hours, filter, filter cake glacial acetic acid ethyl ester 5ml washs, 80 DEG C of dryings, obtain finished product 6.3g, content purity 99.1%.

Embodiment 3

1) by hexone 10g, methane amide 9g, ammonium formiate 12g drop into heat temperature raising in reaction flask, treat interior temperature rise to 150 DEG C, react 20 hours.Question response terminates, and is cooled to 40 DEG C and adds 20ml water, layering, obtain oil reservoir 9g.

2) 9g oil reservoir and the dense HCl of 30ml are dropped into reaction flask, reflux is after 8 hours, evaporated under reduced pressure, obtains solid and adds 20ml water again and start to stir, add 0.3g gac again, be heated to 70 DEG C-80 DEG C, be incubated 30 minutes, filter, filtrate reduced in volume, to dry, adds ethyl acetate 50ml, be cooled to 0 DEG C, crystallization, be incubated 3 hours, filter, filter cake glacial acetic acid ethyl ester 5ml washs, 80 DEG C of dryings, obtain 1,3-dimethyl butyrate amine hydrochlorate finished product 6.3g, content purity 99.3%.

1,3-dimethyl butylamine hydrochloride product of above embodiment all have passed through the detection of NMR, mass spectrum and HPLC.

NMR ultimate analysis (C ₆h ₁₅n.HCl): C52.37%, H11.64%, N10.28%; Theoretical value C52.36%, H11.64%, N10.18%.

The detection of mass spectrum and HPLC: the mass spectrum post selecting Luna C18150*2mm5uM, moving phase is methyl alcohol; Flow velocity: 1.0ml/min, column temperature 30-40 DEG C; Its molecular weight is 137.5, and the purity of 1,3-dimethyl butyrate amine hydrochlorate of the preparation of above-described embodiment is followed successively by: 99.1%, 99.1,99.3%.

1,3-dimethyl butyrate amine hydrochlorate prepared by embodiment 1 carries out HPLC detection, and as shown in figure 1 and table 1, wherein, peak 2 is that 1,3-dimethyl butyrate amine hydrochlorate detecting position is put; Purity is 99.071%.

Table 1HPLC detects real time data

	Retention time	Area	Area percentage	Peak height	Height percent
						Peak 1	2.515	40702	0.823	8610	0.737
Peak 2	2.726	4898073	99.071	1157586	99.066
						Peak 3	3.096	5239	0.106	2305	0.197
Amount to		4944014	100.000	1168501	100

The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.

Claims

The preparation method of 1.1,3-dimethyl butyrate amine hydrochlorate, is characterized in that, comprise the steps:

1) hexone, methane amide and ammonium formiate mixing, reacts 19-21 hour at temperature is 120-170 DEG C;

2), after reaction terminates, remove impurity, obtain middle product a;

3) step 2) in the middle product a of gained and concentrated hydrochloric acid hybrid reaction, heating reflux reaction 7-9 hour, obtains 1,3-dimethyl butyrate amine hydrochlorate.
2. preparation method as claimed in claim 1, is characterized in that, described step 2) in, after reaction terminates, be cooled to 35-45 DEG C, carry out water extraction, remove water layer, obtain middle product a.
3. preparation method as claimed in claim 1, is characterized in that, also comprise the steps:

4) 1, the 3-dimethyl butyrate amine hydrochlorate that prepared by described step 3) concentrates evaporate to dryness, obtains solid product b;

5) aqueous solution of obtained described solid product b, adds gac, 70-80 DEG C of insulation 30-40 minute;

6) filter, filtrate evaporate to dryness concentrates, and obtains product c.
4. preparation method as claimed in claim 1, is characterized in that, also comprise the steps:

7) in step 6), products therefrom c adds ethyl acetate, at-2 DEG C ~ 2 DEG C temperature, and crystallize out, insulation 2.5-3.5 hour, filters;

8) filter cake ethyl acetate is washed, 75-85 DEG C of drying, obtains high purity 1,3-dimethyl butyrate amine hydrochlorate.
5. preparation method as claimed in claim 1, it is characterized in that, the structural formula of described middle product a is:
6. preparation method as claimed in claim 1, is characterized in that: the molar ratio of described hexone, methane amide and ammonium formiate is: 0.3-0.5:1:0.5-1.
7. preparation method as claimed in claim 1, it is characterized in that: in described step 3), the envelope-bulk to weight ratio of concentrated hydrochloric acid and described middle product a is 1:2 ~ 2:5.