A kind of preparation method of vitamin A acetate intermediate C15 and vitamin A acetate

An acetate and intermediate technology, which is applied in the field of preparation of vitamin A acetate intermediate C15 and vitamin A acetate, can solve the problems of complex post-processing, cumbersome preparation process, low yield and purity, etc. The effect of easy control of reaction conditions, high nucleophilic substitution ability, and high reaction selectivity

Active Publication Date: 2022-04-12
XINFA PHARMA
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  • Abstract
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  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0027] In summary, although the C15+C5 route of vitamin A acetate has certain industrial value, the preparation process of the C14 or C15 intermediate used is cumbersome, the post-treatment is complicated, the operation safety is poor, the reaction conditions are harsh, the cost is high, and the atomic Poor economy, large amount of waste water, not environmentally friendly, low yield and purity, so the development and optimization of vitamin A acetate intermediates is of great significance for the industrial production of vitamin A acetate

Method used

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  • A kind of preparation method of vitamin A acetate intermediate C15 and vitamin A acetate
  • A kind of preparation method of vitamin A acetate intermediate C15 and vitamin A acetate
  • A kind of preparation method of vitamin A acetate intermediate C15 and vitamin A acetate

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Effect test

Embodiment 1

[0106] Embodiment 1: Formula III 1 Compound preparation

[0107] Formula III 1 The structural formula of the compound is as follows:

[0108]

[0109] Under nitrogen protection, add 250 grams of acetonitrile, 41.5 grams (0.2 moles) of 1-bromo-2-methyl-4-acetoxy-2-butyl alkene (II 1 ), 52.5 grams (0.2 moles) of triphenylphosphine, stirred and reacted at 60-65°C for 4 hours, cooled to 10-15°C, filtered, and obtained 89.2 grams of formula III after drying the filter cake 1 Compound, the filtrate was calibrated with a liquid-phase external standard method to have a triphenylphosphine content of 2.63 grams, which can be directly applied to the next batch of reactions. The calculated yield based on the actual conversion of triphenylphosphine was 99.9%, and the liquid-phase purity was 99.7%.

Embodiment 2

[0110] Embodiment 2: Formula III 2 Compound preparation

[0111] Formula III 2 The structural formula of the compound is as follows:

[0112]

[0113] Under nitrogen protection, add 250 grams of acetonitrile, 34.1 grams (0.21 moles) of 1-chloro-2-methyl-4-acetoxy-2-butyl alkene (II 2 ), 52.5 grams (0.2 moles) of triphenylphosphine, stirred and reacted at 70-75°C for 4 hours, cooled to 10-15°C, filtered, and obtained 77.8 grams of formula III after drying the filter cake 2 Compound, the filtrate was calibrated with a liquid-phase external standard method to have a triphenylphosphine content of 4.46 grams, which can be directly applied to the next batch of reactions. The calculated yield based on the actual conversion of triphenylphosphine was 99.9%, and the liquid-phase purity was 99.5%.

Embodiment 3

[0114] Embodiment 3: Formula III 3 Preparation of compound (diethyl 2-methyl-4-acetoxy-2-butenylphosphonate)

[0115] Formula III 3 The structural formula of the compound is as follows:

[0116]

[0117] Under nitrogen protection, add 41.5 grams (0.2 moles) of 1-bromo-2-methyl-4-acetoxy-2-butene (II 1 ), 41.6 grams (0.25 moles) of triethyl phosphite, stirred and reacted at 105-110°C for 4 hours (using ethanol to recover the generated by-product bromoethane), cooled to 70-75°C, replaced with a vacuum distillation device, and recovered After excessive triethyl phosphite, further underpressure distillation (110-120 ℃ / 1-2mmHg) obtains 49.6 grams of 2-methyl-4-acetoxy-2-butenyl phosphonic acid diethyl ester (Ⅲ 3 ), the yield is 93.9%, and the gas phase purity is 99.2%.

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Abstract

The invention provides a vitamin A acetate intermediate C15 and a preparation method of vitamin A acetate. The method uses 1-halo-2-methyl-4-acetoxy-2-butene as raw material, and triphenylphosphine or phosphite triester to prepare the corresponding Wittig reagent through substitution reaction, and then react with β-cyclic lemon The aldehyde undergoes Wittig reaction, hydrolyzes the ester group under alkaline conditions, and acidifies to obtain the corresponding halogenated product, and then reacts with triphenylphosphine or phosphite triester again to prepare C15. Vitamin A acetate can be prepared by using the obtained C15 under alkaline conditions and 2-methyl-4-acetoxy-2-butenal through Wittig reaction. The method of the invention has single reaction types, easy operation and realization of reaction conditions, safe and environment-friendly operation, simple post-treatment, and low cost; strong reactivity, high reaction selectivity, high atom economy, and high yield and purity of target products.

Description

technical field [0001] The invention relates to a vitamin A acetate intermediate C15 and a preparation method of vitamin A acetate, belonging to the technical fields of fine chemical industry and medicine. Background technique [0002] Vitamin A and its derivatives are an important class of pharmaceuticals and feed additives, and the most commonly used vitamin A derivative is vitamin A acetate. Vitamin A acetate, also known as vitamin A acetate, retinyl acetate, vitamin A acetate, CAS number 127-47-9, is a light yellow solid powder with good fluidity. The structural formula of vitamin A acetate is as follows: [0003] [0004] vitamin A acetate [0005] Vitamin A acetate has a variety of important physiological functions, and is an essential nutrient for vision system, growth, epithelial tissue and bone development, sperm production and fetal growth and development. Vitamin A acetate plays an important role in many life activities, such as vision generation, growth, de...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07F9/54C07F9/40C07C67/293C07C69/145C07C17/093C07C22/02
CPCC07F9/5442C07F9/4006C07C67/293C07C17/093C07C2601/16C07C69/145C07C22/02
Inventor 戚聿新江枭南腾玉奇刘思尧
Owner XINFA PHARMA
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