Gestodene synthesis
- Product Name:Gestodene
- CAS Number:60282-87-3
- Molecular formula:C21H26O2
- Molecular Weight:310.43
Yield:60282-87-3 8.17 g
Reaction Conditions:
Stage #1:15α-Acetoxy-18-methyl-4-estren-3,17-dion with hydrogenchloride;propylene glycol in 1,4-dioxane;1,2-dimethoxyethane at -20; for 4 h;
Stage #2: with toluene-4-sulfonic acid;trimethyl orthoformate in methanol at 20; for 3 h;
Stage #3:acetyleneFurther stages;
Steps:
Example
1, in the preparation of compound 2aTo a dried reaction flask was charged four 10g13β- ethyl acetoxy -15α- - steroid-4-ene-3,17-dione, 150 mL of ethylene glycol dimethyl ether, 1,2-propanediol 2.5mL, 1.1mL dioxane / hydrochloric acid, the reaction at -20 4 hours, the reaction was added 20mL of triethylamine was terminated, the solvent was evaporated, ethyl acetate was added dissolved, and water extraction, stratification, the organic phase was collected, concentrated to Add to dry isopropyl ether crystallization, filtration, drying, 10.8g compound 2a, molar yield of 92%.
2 preparation of compound 3aThe 15mL trimethylorthoformate and 0.1g p-toluenesulfonic acid was added to 100mL of methanol solution containing 15g of compound 2a, and stirred at room temperature; when TLC monitored the reaction was complete (about 3 hours), the reaction was cooled to 0 , large amount of solid precipitation, temperature and stirring was continued for 1 hour and filtration, the filter cake washed with a small amount of methanol and vacuum freeze drying, 12.5g compound 3a, molar yield of 98%.
Preparation 3, the compound 4aTo a dry reaction flask four 700mL of tetrahydrofuran, 35g potassium t-butoxide, down to -2 ~ 2 , pass gas and acetylene was added 70g compound 3a, to continue through the acetylene reaction was complete (about 1 hour), and then slowly drops aqueous ammonium chloride solution into 560mL of 25wt% (on precooled to 10 deg.] C), the control system of the dropwise addition the temperature does not exceed 25 ; dropwise completion, ethyl acetate was added 360mL stratified extraction, the organic phase was collected, the solvent was concentrated and dried , that was 71.5g compound 4a, a molar yield of 95.1%.
4, gestodene (Compound 1) Preparation ofTo the reaction flask was added 10g of compound 4a and 100mL of methanol was added with stirring concentration 6mol / L aqueous hydrochloric acid, and lower in 13 ~ 17 for 1 hour, the reaction mixture was added dropwise to purified water 120mL, dropping time of 50min, stirring was continued and then stirred at room temperature for one hour, filtered, and the solid was collected, washed with water until neutral, dried to obtain 8.17g yellow solid gestodene (compound 1), the molar yield of 97.0%, HPLC purity 99.2% .
References:
Shanghai Acebright Pharmaceuticals Group Co., Ltd;An, Xiaoxia;Mao, Fengwang;Zhao, Jiangyong;Huang, Chengjun CN105237605, 2016, A Location in patent:Paragraph 0041-0058
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