CN117603064A - Preparation method and intermediate of tri (hydroxyalkyl) methylamine - Google Patents

Preparation method and intermediate of tri (hydroxyalkyl) methylamine Download PDF

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Publication number
CN117603064A
CN117603064A CN202311483348.6A CN202311483348A CN117603064A CN 117603064 A CN117603064 A CN 117603064A CN 202311483348 A CN202311483348 A CN 202311483348A CN 117603064 A CN117603064 A CN 117603064A
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compound
hydroxyalkyl
methylamine
tri
tris
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陆茜
匡逸
汪海明
陆学友
沈国军
张婷
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Shanghai Linkchem Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C07C215/10—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with one amino group and at least two hydroxy groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses a preparation method of tri (hydroxyalkyl) methylamine and an intermediate thereof, belonging to the field of organic synthesis. The invention provides a novel intermediate for synthesizing tri (hydroxyalkyl) methyl amine, namely a compound 4, which is utilized to react with ozone and a reducing agent in sequence to obtain a novel intermediate compound 5; then deprotecting the amino group to obtain the target of formula 6The standard, tris (hydroxyalkyl) methylamine. The method is simpler, is more suitable for industrialization, and can obtain a series of tri (hydroxyalkyl) methyl amine by only changing the carbon chain length of the raw material.

Description

Preparation method and intermediate of tri (hydroxyalkyl) methylamine
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of tri (hydroxyalkyl) methylamine and an intermediate thereof.
Background
Tri (hydroxyalkyl) methylamine refers to a series of compounds including tri (hydroxymethyl) methylamine, tri (2-hydroxyethyl) methylamine, tri (3-hydroxypropyl) methylamine. Most of the series of compounds have similar chemical properties and have wide application prospect.
According to literature reports, tris (hydroxyalkyl) methylamines can be used to prepare buffer solutions with acidic reagents such as hydrochloric acid (e.g. journal literature Li D, chen R, zhu X, et al light fueled mixing in open surface droplet microfluidics for rapid probe preparation [ J ]. Physical chemistry chemical physics,2021,23 (46): 26356-26365) or to form new crystalline forms of some drugs with active agents bearing carboxylic acid groups (e.g. patent literature US 20110230524).
In the prior art, george R.Newkome et al (George R.Newkome, charles N.Moorefield, et A Convenient Synthesis of "Bis-homotris":4-Amino-4- [1- (3-hydropropyl) ] -1,7-heptanediol and 1-Azoniaapepellane [ J ]. J.Org.chem.1988,53, 5552-5554.) reported a process that could be used to prepare tris (3-hydroxypropyl) methylamine, the reaction scheme being as follows:
from the above formula, it is known that since the starting material is acrylonitrile, it cannot be used for preparing tris (hydroxymethyl) methylamine or tris (2-hydroxyethyl) methylamine, is not universal, and it is also described that the first reaction step is strongly exothermic, and thus is not suitable for industrial production.
D.W.Moire et al (CN 104254516A) report a process for preparing tri (hydroxymethyl) methylamine by reacting formaldehyde with nitromethane as starting materials to obtain tri (hydroxymethyl) nitromethane, and reducing the nitro group to obtain tri (hydroxymethyl) methylamine. However, this approach is limited to the preparation of tris (hydroxymethyl) methylamine, and if an aldehyde with a longer carbon chain is used instead of formaldehyde (such as acetaldehyde), the result is a product with the hydroxyl group at the beta position of the nitro group, rather than the alkyl end position.
Disclosure of Invention
The present invention has been made to solve the above-described problems, and an object of the present invention is to provide a process for producing tri (hydroxyalkyl) methylamines which can be used for producing a wider variety of tri (hydroxyalkyl) methylamines, and an intermediate for synthesizing tri (hydroxyalkyl) methylamines using the process.
The invention provides a preparation method of tri (hydroxyalkyl) methyl amine, which has the characteristics that the preparation method comprises the following reaction steps:
in the above formula, PG is an amino protecting group, x and y are independently selected from any integer between 0 and 5,
step 1, sequentially reacting a compound 4 with ozone and a reducing agent to obtain a compound 5;
step 2, reacting the compound 5 with an amino protecting group removal reagent to obtain a compound 6.
In one embodiment of the invention, x=y=0 or 1.
In one embodiment of the invention, the reducing agent is a metal complex hydrogen compound. The metal complex hydrogen compound is selected from any one or more of sodium borohydride, potassium borohydride, lithium aluminum hydride and sodium thiosulfate.
In one embodiment of the invention, the amino protecting group is selected from the group consisting of benzyloxycarbonyl, t-butyloxycarbonyl, fluorenylmethoxycarbonyl, p-methoxybenzyl, benzyl, trityl, p-toluenesulfonyl, phthaloyl, allyloxycarbonyl.
In one embodiment of the invention, in the step 1, the compound 4 is mixed with the organic solvent 1 and the alkali reagent, the temperature is controlled between minus 50 ℃ and minus 80 ℃ (specifically, minus 78 ℃), and ozone is introduced for reaction; after the reaction is finished, the temperature is returned to 0 ℃ -10 ℃ (specifically, the temperature can be selected to be 0 ℃), an organic solvent 2 and a reducing agent are added, and then the temperature is raised to room temperature for reaction, so that the compound 5 is obtained.
In one embodiment of the present invention, the concentration condition of the compound 4 with respect to the organic solvent 1 is 0.2 to 0.5mol/L; specifically, the concentration of the catalyst is 0.35mol/L.
In one embodiment of the present invention, the organic solvent 1 and the organic solvent 2 are respectively and independently selected from one or two of methanol and dichloromethane. Wherein, the organic solvent 1 and the organic solvent 2 are preferably the combination of methanol and methylene dichloride, and the volume ratio of the two is 1:1.
In one embodiment of the present invention, the volume ratio of the organic solvent 1 to the organic solvent 2 is 2:1.
In one embodiment of the invention, the alkaline agent is selected from any one or more of sodium bicarbonate, sodium carbonate or sodium hydroxide. The molar ratio of the alkali reagent to the compound 4 is (2-4): 1.
in one embodiment of the invention, the molar ratio of the reducing agent to compound 4 (8-15): 1. and particularly, the ratio of the components is 10:1.
In one embodiment of the present invention, when the amino protecting group is benzyloxycarbonyl or benzyl, compound 5 is dissolved in organic solvent 3 in step 2, followed by a heating reaction with Pd/C/hydrogen as the amino deprotection reagent.
In one embodiment of the present invention, the organic solvent 3 is an alcohol solvent, preferably methanol and/or ethanol.
The invention provides an intermediate for synthesizing tri (hydroxyalkyl) methyl amine, the structure of which is shown as formula 4:
in the above formula, PG is an amino protecting group, and x and y are independently selected from any integer between 0 and 5.
In one embodiment of the invention, PG is carbobenzoxy or t-butoxycarbonyl.
In one embodiment of the present invention, x=y=1.
In one embodiment of the present invention, the preparation process of the above intermediate includes:
wherein X is halogen (Br, cl, I), X and y are independently selected from any integer between 0 and 5;
A. firstly, reacting a compound 1 with a compound 2 to obtain a compound 3;
B. compound 3 is then reacted with an amino protecting reagent to afford compound 4.
In one embodiment of the invention, in the step A, the compound 2 is dispersed in tetrahydrofuran solution, cooled to-10-5 ℃, then diethyl ether solution of the compound 1 is added dropwise, and then the mixture is heated to 40-60 ℃ for reaction for a period of time to obtain the compound 3.
In one embodiment of the present invention, after the reaction is completed, the reaction solution is mixed with a saturated aqueous ammonium chloride solution, then the mixture is subjected to extraction by adjusting the pH to 3 to 4, and the organic phase is collected and then concentrated to give compound 3.
In one embodiment of the invention, the molar ratio of compound 1 to compound 2 in step A is 1 (2-3).
In one embodiment of the invention, the concentration of the diethyl ether solution of compound 1 in step A is between 0.3 and 1.0g/mL. Specifically, 0.5g/mL is selected.
In one embodiment of the invention, the concentration of compound 2 dispersed in the tetrahydrofuran solution in step a is 0.8 to 1.5mol/L; specifically, 1.0mol/L is selected.
In one embodiment of the present invention, compound 3 is dispersed in a solvent, and then a base reagent and an amino protecting reagent are added to the mixture to react with each other in step B.
In one embodiment of the invention, the molar ratio of the base reagent, amino protecting reagent to compound 3 is (2-4): (1-2): 1.
in one embodiment of the present invention, the base reagent is diisopropylethylamine, triethylamine. The amino protecting reagent is selected from any one of benzyl chloroformate, tert-butyl chloroformate and di-tert-butyl dicarbonate.
The invention provides an intermediate for synthesizing tri (hydroxyalkyl) methyl amine, the structure of which is shown as formula 5:
in the above formula, PG is an amino protecting group, and x and y are independently selected from any integer between 1 and 5.
In one embodiment of the invention, PG is carbobenzoxy or t-butoxycarbonyl.
In one embodiment of the present invention, x=y=1.
Effects and effects of the invention
According to the preparation method of the tri (hydroxyalkyl) methyl amine, because the terminal alkenyl compound is treated by using the ozone/reducing agent, the terminal alkenyl compound can be converted into hydroxyl with one less carbon atom, so the preparation method provided by the invention is simpler, more suitable for industrialization, and more universal in comparison with the prior art, a series of tri (hydroxyalkyl) methyl amines can be obtained by only changing the carbon chain length of the raw materials.
Drawings
FIG. 1 is a high performance liquid chromatogram of compound 6a produced in example 4;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrum of the compound 6a produced in example 4.
Detailed Description
In order to make the technical means, the creation features, the achievement of the purpose and the effect of the present invention easy to understand, the present invention is specifically described below with reference to the embodiments and the drawings.
In the examples below, each of the raw materials was a commercially available product unless otherwise specified.
Example 1 ]
Process for the preparation of Compound 3a
This example provides a process for the preparation of compound 3a, having the following formula:
the method comprises the following steps:
under the protection of nitrogen, 3.36L of tetrahydrofuran solution (1.0 mol/L) of the compound 2a is added into a reaction vessel, the temperature is reduced to 0 ℃, 200mL of diethyl ether solution (500 g/L,1.49 mol) of the compound 1a is dropwise added into the reaction vessel, after the dropwise addition is finished, the temperature is increased to 45 ℃ and the reaction is stirred for 4 hours, TLC detection reaction is complete, the reaction solution is poured into 5L of saturated ammonium chloride aqueous solution, 2mol/L of hydrochloric acid aqueous solution is used for regulating the pH value to 3, the organic phase is extracted, anhydrous sodium sulfate is used for drying, and decompression concentration is carried out, so that 158.5g of the compound 3a is obtained, the yield is 70.3%, and the product is light yellow oily and can be directly used in the next step without further purification.
1 H NMR(400MHz,Chloroform-d)δ5.79(ddt,J＝17.5,10.2,7.5Hz,3H),5.14–4.96(m,6H),2.06(d,J＝7.5Hz,6H).
Example 2 ]
Process for the preparation of Compound 4a
This example provides a process for the preparation of compound 4a, having the following formula:
the method comprises the following steps:
150g of compound 3a (0.99 mol,1.0 eq) were dissolved in 2L of methylene chloride, 385g of diisopropylethylamine (2.98 mol,3.0 eq) and 280g of benzyl chloroformate (1.64 mol,1.66 eq) were added in this order, and the mixture was stirred at 25℃for 3h. TLC detection showed that the reaction was complete, and 750mL of 2mol/L aqueous hydrochloric acid was added to extract, the organic phase was taken, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under pressure, and column-chromatographed to give 180.0g of compound 4a, yield 63.7% as a yellow liquid.
LCMS:m/z(ESI),[M+H] + ＝286.
1 H NMR(400MHz,DMSO-d6)δ7.39–7.28(m,5H),6.90(s,1H),5.81–5.67(m,3H),5.11–4.97(m,8H),2.32(d,J＝7.2Hz,6H).
< example 3-1>
Process for preparing compound 5a
This example provides a process for the preparation of compound 5a, having the following formula:
the method comprises the following steps:
200g of compound 4a (0.70 mol,1.0 eq) and 1L of methanol were added to 1L of methylene chloride, 176.4g of sodium hydrogencarbonate (2.10 mol,3.0 eq) were added, the temperature was lowered to-78℃and ozone was introduced (at a rate of 1L/min, 10 hours of continuous introduction) and the reaction mixture was blue and stirred for 10 hours (from the time of introduction of ozone).
The resulting reaction solution was warmed to 0℃and then 0.5L of methanol and 0.5L of methylene chloride were added thereto, 266g of sodium borohydride (7.0 mol,10.0 eq) was added thereto, and the temperature was raised to 25℃and the reaction was stirred for 2 hours.
LCMS detection reaction was complete, ice water bath was cooled to 0 ℃, pH was adjusted to 5 using 4mol/L aqueous hydrochloric acid, filtered using celite, filtrate was concentrated, column chromatography to give 172g of compound 5a, yield 82.6% as colorless liquid.
LCMS:m/z(ESI),[M+H] + ＝298.
1H NMR(400MHz,Methanol-d4)δ7.36–7.29(m,5H),5.01(s,2H),3.65(t,J＝7.1Hz,6H),1.98(t,J＝7.2Hz,6H).
< example 3-2>
Process for preparing compound 5a
This example provides a process for the preparation of compound 5a, having the following formula:
the method comprises the following steps:
200g of Compound 4a (0.70 mol,1.0 eq) was added to 2L of methylene chloride, 176.4g of sodium bicarbonate (2.10 mol,3.0 eq) was added, the temperature was lowered to-78℃and ozone was introduced (at a rate of 1L/min, 10h was continuously introduced), the reaction mixture was blue, and the reaction was stirred for 10h (from the time when ozone was introduced).
The resulting reaction mixture was warmed to 0℃and 1L of methanol was added thereto, 266g of sodium borohydride (7.0 mol,10.0 eq) was added thereto, and the temperature was raised to 25℃and the reaction was stirred for 2 hours.
LCMS detection reaction was complete, ice water bath was cooled to 0 ℃, pH was adjusted to 5 using 4mol/L aqueous hydrochloric acid, filtered using celite, the filtrate was concentrated, column chromatography to give 144.7g of compound 5a, yield 69.5% colorless liquid.
Example 4 ]
Process for the preparation of Compound 6a
This example provides a method for preparing compound 6a, which has the following reaction formula:
the method comprises the following steps:
70g of compound 5a was dissolved in 700mL of methanol, 7g of 10wt% palladium on carbon catalyst was added to replace hydrogen, the reaction vessel was allowed to be under a hydrogen atmosphere, heated to 40℃and stirred for reaction for 5 hours. TLC monitoring showed the reaction was complete, filtered through celite, and concentrated under reduced pressure to remove the solvent to give 31.5g of compound 6a in 82% yield, 99.9% purity as a white solid.
The high performance liquid chromatogram and the hydrogen chromatogram of the compound 6a are shown in figures 1-2.
HPLC (ELSD) rt=1.844 min with HPLC purity 99.9%.
1 H NMR(400MHz,DMSO-d6)δ3.87(s,5H),3.52(t,J＝6.9Hz,6H),1.51(t,J＝6.9Hz,6H).
Effects and effects of the examples
According to the preparation method of the tri (hydroxyalkyl) methyl amine, which is related to the embodiment, because the terminal alkenyl compound is treated by using ozone/reducing agent, the terminal alkenyl compound can be converted into hydroxyl groups with one less carbon atom, so the preparation method provided by the invention is simpler, more suitable for industrialization, and more universal compared with the prior art, a series of tri (hydroxyalkyl) methyl amines can be obtained by only changing the carbon chain length of the raw materials.
Further, in the above embodiment, after the ozonolysis reaction, the peroxide formed by the reaction is not treated by the traditional reducing agents such as zinc powder/acid, trimethyl phosphite and the like, but sodium borohydride is creatively selected, so that the peroxide formed after the ozonolysis is directly converted into hydroxyl groups instead of aldehyde groups, and the reaction steps are greatly saved.
Further, since the above examples selected methanol and methylene chloride as mixed solvents in the steps of ozonolysis and subsequent reduction reactions, higher yields were obtained than with a single solvent.
The above examples are provided as preferred embodiments of the present invention and are not intended to limit the scope of the invention, nor the order of execution of the steps described. The present invention is obviously modified by a person skilled in the art in combination with the prior common general knowledge, and falls within the scope of protection defined by the claims of the present invention.

Claims (10)

1. A process for the preparation of tris (hydroxyalkyl) methylamines, comprising the following reaction steps:
in the above formula, PG is an amino protecting group, x and y are independently selected from any integer between 0 and 5,
step 1, sequentially reacting a compound 4 with ozone and a reducing agent to obtain a compound 5;
step 2, reacting the compound 5 with an amino protecting group removal reagent to obtain a compound 6.
2. The method for producing tri (hydroxyalkyl) methylamine as claimed in claim 1, wherein:
wherein, the preparation method of the compound 4 comprises the following steps:
in the formula, X is selected from any one of chlorine, bromine or iodine,
reacting compound 1 with compound 2 to give compound 3;
compound 3 is reacted with an amino protecting reagent to give compound 4.
3. The method for producing tri (hydroxyalkyl) methylamine as claimed in claim 1, wherein:
where x=y=0 or 1.
4. The method for producing tri (hydroxyalkyl) methylamine as claimed in claim 1, wherein:
wherein the reducing agent is a metal complex hydrogen compound.
5. The method for producing tri (hydroxyalkyl) methylamine as claimed in claim 4, wherein:
wherein the metal complex hydrogen compound is selected from any one or more of sodium borohydride, potassium borohydride, lithium aluminum hydride and sodium thiosulfate borohydride.
6. A process for the preparation of tris (hydroxyalkyl) methylamines as claimed in claim 1, wherein,
wherein the amino protecting group is selected from the group consisting of benzyloxycarbonyl, t-butyloxycarbonyl, fluorenylmethoxycarbonyl, p-methoxybenzyl, benzyl, trityl, p-toluenesulfonyl, phthaloyl, allyloxycarbonyl.
7. An intermediate for the synthesis of tris (hydroxyalkyl) methylamines, characterized by the following structural formula:
in the above formula, PG is an amino protecting group, and x and y are independently selected from any integer between 0 and 5.
8. An intermediate for the synthesis of tris (hydroxyalkyl) methylamines, characterized by the following structural formula:
in the above formula, PG is an amino protecting group, and x and y are independently selected from any integer between 1 and 5.
9. An intermediate for the synthesis of tris (hydroxyalkyl) methylamines as claimed in claim 7 or 8, wherein: wherein PG is carbobenzoxy or t-butoxycarbonyl.
10. An intermediate for the synthesis of tris (hydroxyalkyl) methylamines as claimed in claim 7 or 8, wherein: where x=y=1.
CN202311483348.6A 2023-11-08 2023-11-08 Preparation method and intermediate of tri (hydroxyalkyl) methylamine Pending CN117603064A (en)

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