Protecting group effect on the 1,2-dehydrogenation of 19-hydroxysteroids: a highly efficient protocol for the synthesis of estrogens

Tetrahedron Letters

Volumn 51, Issue 24, 2010, Pages 3242-3245

  Jing, Yu ^a   Xu, Cheng Gong ^b   Ding, Kai ^b   Lin, Jing Rong ^a   Jin, Rong Hua ^a   Tian, Wei Sheng ^a,b  

^a SHANGHAI NORMAL UNIVERSITY   (China)

^b SHANGHAI INSTITUTE OF ORGANIC CHEMISTRY   (China)

Author keywords

Dehydrogenation; Estrogen; Retro aldol reaction; Steroid

Indexed keywords

19 HYDROXYSTEROID DERIVATIVE; ESTROGEN DERIVATIVE; HYDROXYSTEROID; OXIDIZING AGENT; UNCLASSIFIED DRUG;

ACYLATION; ALDOL REACTION; AROMATIZATION; ARTICLE; DEHYDROGENATION; ESTROGEN SYNTHESIS; QUANTUM YIELD; REACTION ANALYSIS; REACTION TIME;

EID: 77953597725     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2010.04.070     Document Type: Article

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31. Direct oxidation of 1a formed a by-product, which can only be removed by recrystallization and resulted in decrease of isolated yield (40-50%).{A figure is presented}
32. Preparation of 6,7-dehydroestrone: According to the previous procedure, 300 mg of 1a (1 mmol) provided crude acetyl ester 1h (390 mg), which was used without further purification.The mixture of crude acetyl ester 1h (390 mg) and chloranil (417 mg, 1.70 mmol) in t-BuOH (10 mL) was refluxed for 2 h, then the solvent was removed under reduced pressure and the residue was dissolved in MeOH (30 mL). The insoluble portion was removed by filtration and washed with MeOH (3 × 10 mL). Solvent removal afforded the acetyl ester 4 (550 mg) as a yellow oil, which was used without further purification. According to the previous procedure, dehydrogenation of crude 4 with DDQ and subsequent acid-catalyzed hydrolysis provided 6,7-dehydroestrone (184 mg, 69% from 1a) as a white powder after purification by column chromatography.According to the previous procedure, dehydrogenation of crude 4 with DDQ and subsequent acid-catalyzed hydrolysis provided 6,7-dehydroestrone (184 mg, 69% from 1a) as a white powder after purification by column chromatography.
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35. General procedure for the preparation of compound 6a: To a solution of steroid 2h (200 mg, 0.58 mmol) and TsOH (20 mg, 0.10 mmol) in dry MeOH (3 mL), trimethyl orthoformate (1 mL) was added slowly. The mixture was heated for 1 h (60 °C). After completion (monitored with TLC), the solvent was removed under reduced pressure. The resulting residue was purified by column chromatography to afford estrone 3-methyl ether 6a (136 mg, 82%).