Synthetic preparation method of stable isotope labeled phenylethanolamine A

A stable isotope and phenylethanolamine technology, which is applied in the preparation of carbon-based compounds, organic compounds, and aminohydroxyl compounds, can solve the problems of high price and high detection cost, and achieve fewer experimental steps and lower detection costs , The effect of low preparation cost

Inactive Publication Date: 2020-10-16
SHANGHAI ANPEL SCI INSTR
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this method requires the use of stable isotope-labeled phenylethanolamine A as an internal standard. This internal standard is completely dependent on imports, and the price is extremely expensive, resulting in high detection costs.
There are no relevant documents and patents at home and abroad to report the synthesis method of stable isotope-labeled phenylethanolamine A

Method used

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  • Synthetic preparation method of stable isotope labeled phenylethanolamine A
  • Synthetic preparation method of stable isotope labeled phenylethanolamine A
  • Synthetic preparation method of stable isotope labeled phenylethanolamine A

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preparation example Construction

[0027] The synthetic preparation method of the stable isotope-labeled phenylethanolamine A provided by the present invention comprises the following steps:

[0028] S1) p-Nitrobenzaldehyde is first combined with acetyltriphenylphosphine, and then reduced by trichlorosilane to obtain the compound shown in formula 1;

[0029]

[0030] S2) the compound of formula 1 undergoes reductive amination reaction to obtain the compound shown in formula 2;

[0031]

[0032] S3) bromo-p-hydroxyacetophenone and deuterated methanol are reacted by Mitsunobu to obtain deuterium-labeled bromo-p-methoxyacetophenone shown in formula 3;

[0033]

[0034] S4) The compounds of formula 2 and formula 3 are subjected to a nucleophilic reaction in methanol, and directly reduced with a hydroboration reagent to obtain the stable isotope-labeled phenylethanolamine A of the target compound, the structural formula is as follows:

[0035]

[0036] The synthetic route of the stable isotope-labeled p...

Embodiment 1

[0040] (1) Dissolve 6.04g of p-nitrobenzaldehyde and 12.75g of acetyltriphenylphosphine in 60mL of dichloromethane, react at 50°C for 12 hours, then cool to room temperature, add 8mL of trichlorosilane to the solution, and react at room temperature for 24 hours . At the end, add 120 mL of saturated NaHCO 3 , after stirring for 2 hours, suction filtration. Then the aqueous phase was extracted with ethyl acetate, a total of 2 extractions, 60 mL each time, the organic phases were combined, dried with anhydrous sodium sulfate, filtered with suction, the solvent was removed by rotary evaporation, and purified by chromatography. The eluent used was a mixture of n-hexane and ethyl acetate at a molar ratio of 4:1 to obtain 6.64 g of the compound of formula 1 with a yield of 86.7%.

[0041] (2) After dissolving 2.15 g of the compound of formula 1 in 28 mL of 2M ethanol-ammonia solution, add 6.67 mL of isopropyl titanate and react at room temperature for 6 hours. Subsequently, the re...

Embodiment 2

[0045] (1) Dissolve 12g of p-nitrobenzaldehyde and 25.5 g of acetyltriphenylphosphine in 120 mL of dichloromethane, react at 70°C for 6 hours, then add 16 mL of trichlorosilane to the solution, and finish the reaction after 6 hours. Then add 300 mL saturated NaHCO 3 , after stirring for 2 hours, the aftertreatment was the same as step 1 in Example 1 to obtain 10.5 g of the compound of formula 1 with a yield of 68.4%.

[0046] (2) After 10.5 g of the compound of formula 1 was dissolved in 150 mL of 2M methanol-ammonia solution, 35 mL of isopropyl titanate was added and reacted under ice-cooling for 12 hours. Subsequently, 3.5 g of sodium borohydride was added, and after the addition was completed, the reaction was returned to room temperature for 3 hours. Subsequently, 50 mL of saturated sodium carbonate solution was added, and after stirring for 2.5 hours, the aftertreatment was the same as step 2 in Example 1 to obtain 9.46 g of the compound of formula 2 with a yield of 90.1...

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Abstract

The invention discloses a synthetic preparation method of stable isotope labeled phenylethanolamine A. The synthetic preparation method comprises the following steps of: S1) firstly reacting p-nitrobenzaldehyde with acetyltriphenylphosphine, and then conducting reducing by trichlorosilane to obtain a compound shown as formula 1; S2) carrying out reductive amination reaction on the compound shown as formula 1 to obtain a compound shown as formula 2; S3) subjecting bromo-p-hydroxyacetophenone and deuterated methanol to Mmitsunobu reaction so as to obtain deuterium-labeled bromo-p-methoxyacetophenone shown as formula 3; and S4) carrying out nucleophilic reaction on the compounds shown as formula 2 and formula 3 in methanol, and directly performing reduction by using a hydroboration reagent toobtain the target compound stable isotope labeled phenylethanolamine A. According to the method, cheap p-nitrobenzaldehyde and p-hydroxyacetophenone are used as the raw materials, phenylethanolamineA with purity and abundance both up to 98% or above can be prepared through simple synthesis of four steps, the experiment steps are few, the operation is simple, and the detection cost is greatly reduced.

Description

technical field [0001] The invention relates to a method for synthesizing organic compounds, in particular to a method for synthesizing and preparing stable isotope-labeled phenylethanolamine A. Background technique [0002] Phenylethanolamine A, also known as "Clonpamine", is an adrenaline stimulant such as β-receptor agonists, and was mainly used to treat bronchitis and asthma at first. Subsequent biological activity and application found that the compound can promote protein synthesis. Therefore, livestock farmers use it as a growth promoter and add it to feed to reduce the fat of livestock, increase the proportion of lean meat, and improve the feed conversion rate. Such substances have been included in the catalog of lean meat products. At the same time, the researchers also found that after the livestock were fed with phenylethanolamine A, the drug would accumulate in the livestock, and once consumed by humans, it would pose a great health risk. When people eat pork ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C213/00C07C217/70
CPCC07C201/12C07C209/28C07C213/00C07C45/64C07B2200/05C07C205/45C07C211/29C07C217/70C07C49/84
Inventor 陈武炼徐敏
Owner SHANGHAI ANPEL SCI INSTR
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