- Preparation method of altrenogest
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The invention discloses a preparation method of altrenogest, and belongs to the technical field of preparation and processing of pharmaceutical compounds. The method comprises the following steps: firstly, dissolving 3-protected estrogen-delta, delta-diene-17-one (1) in an organic solvent, and carrying out Grignard reaction to obtain 3-protected 17beta-hydroxyl-17alpha-propenyl-estra-delta, delta-diene (2); then carrying out hydrolysis reaction to obtain a dichloromethane solution of 17 beta-hydroxyl-17 alpha-propenyl estra-3-one-delta, delta-diene (3), and finally carrying out dehydrogenation reaction to obtain altrenogest. The method has the advantages of complete reaction, clear reaction complete judgment standard and few byproducts; reaction products in each step are easy to purify, the total mass yield of a final product is higher than 75%, and the purity reaches 99% or above; the method has the advantages of cheap and accessible raw materials, low cost, high operability and extremely high commercial competitiveness, is suitable for industrial large-scale production, and has favorable economic benefits.
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- Efficient synthesis method for altrenogest
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The invention relates to an efficient synthesis method for altrenogest and belongs to the technical field of veterinary drugs. The synthesis method disclosed by the invention comprises the following steps: S1, preparing an intermediate XY-1 from estra-4,9-diene-3,17-dione (SM) as a starting raw material under the actions of lithium diisopropylamide (LDA) and trimethylchlorosilane ((CH3)3SiCl); S2,subjecting the intermediate XY-1 and allylmagnesium bromide to a grignard reaction to obtain an intermediate XY-2; and S3, carrying out dual-bond rearrangement and unprotected radical reaction on theintermediate XY-2 under the action of a deprotector to obtain crude altrenogest, and carrying out recrystallization and purification to obtain high-purity altrenogest. The altrenogest product prepared by using the efficient synthesis method is high in yield and product purity; virulent reactions are not adopted in the whole process route; in addition, various reagents are relatively cheap and available, and it is to realize large-scale amplification.
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Paragraph 0013; 0036; 0043-0045; 0048; 0055-0057; 0060; 0067
(2019/02/04)
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- Synthetic method of altrenogest
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The invention discloses a synthetic method of altrenogest. The synthetic method comprises following steps: in an alcoholic solvent, an acid A and a compound M are added at 0 to 25 DEG C, an obtained mixture is heated to 30 to 90 DEG C for 5 to 24h of reaction, is cooled to room temperature, and then is subjected to distillation so as to remove the solvent; tetrahydrofuran is added, an obtained product is added at -10 to 10 DEG C, CH2CHCH2MgX is added dropwise, an obtained mixed product is heated to 25 to 60 DEG C for 2 to 5h of reaction, and then is cooled until the temperature is lower than 0 DEG C, an acid B is added dropwise so as to adjust pH value to 1 to 3, and then an obtained mixed material is heated to 60 DEG C for 5h of reaction; stirring is carried out for layering, an obtained upper layer product is subjected to drying and concentration with anhydrous sodium sulfate, and is refrigerated at a temperature of 5 DEG C or lower; recrystallization is carried out so as to obtain altrenogest. According to the synthetic method, altrenogest is prepared via one-pot method, the raw materials are easily available, the synthetic method is simple, and is friendly to the environment, cost is low, yield is high, and the synthetic method is especially suitable for industrialized production.
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Paragraph 0042-0043
(2017/09/01)
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- Synthetic method of altrenogest
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The invention discloses a synthetic method of altrenogest, comprising subjecting the compound 3-ethylenedioxy-estra-5,10-diene-17-one as raw material to Grignard reaction with allyl Grignard reagent to obtain 17-Beta-hydroxy-17-Alpha-allyl-3-ethylenedioxy-estra-5,10-diene; performing deprotection transposition to obtain 17-Beta-hydroxy-17-Alpha-allyl-estra-5,10-diene-3-one; performing dehydrogenation to obtain crude altrenogest, and refining to obtain fine altrenogest. The synthetic route is simple and handy, materials used in the reaction process are cheap, the process is stable, and the synthetic method is suitable for industrial large-scale production.
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Paragraph 0018-0019
(2017/08/29)
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- Synthesis method of altrenogest
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The invention relates to a synthesis method of altrenogest. The synthesis method comprises the following steps: using Estra-4,9-diene-3,17-dione as a raw material, protecting 3-carbonyl in the form of ketal, then reacting 17-carbonyl with allylmagnesium bromide, deprotecting, and oxidizing to construct a 11,12-carbon-carbon double-bond reaction, thus synthesizing the altrenogest. The synthesis method provided by the invention has the advantages of accessible raw materials, simple process, environment friendliness, low cost and high yield.
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