1-Hydroxydehydroepiandrosterone → (Z)-1alpha,3beta-pregna-5,17(20)-diene-1,3-diol

HRID 1105842

반응식

HRID 1105842 반응식
[CH3:1][C@@:2]12[C:10](=O)[CH2:9][CH2:8][C@H:7]1[C@@H:6]1[CH2:12][CH:13]=[C:14]3[CH2:19][C@@H:18]([OH:20])[CH2:17][C@H:16]([OH:21])[C@:15]3([CH3:22])[C@H:5]1[CH2:4][CH2:3]2.[CH3:23][C:24](C)([O-])C.[K+]>[I-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.O1CCCC1>[CH3:23]/[CH:24]=[C:10]1/[CH2:9][CH2:8][C@@H:7]2[C@:2]/1([CH3:1])[CH2:3][CH2:4][C@H:5]1[C@H:6]2[CH2:12][CH:13]=[C:14]2[C@:15]1([CH3:22])[C@@H:16]([OH:21])[CH2:17][C@H:18]([OH:20])[CH2:19]2

참가 물질

5

반응물 2

HCID 1679551-HydroxydehydroepiandrosteroneHCID 23665647Potassium tert-butoxide

생성물 1

HCID 70476101(Z)-1alpha,3beta-pregna-5,17(20)-diene-1,3-diol

시약·촉매·용매 2

HCID 78474Ethyltriphenylphosphonium iodide촉매HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred suspension of 9.12 g (30 mmol) of 1α-hydroxydehydroepiandrosterone and 25.1 g (60 mmol) of ethyltriphenylphosphonium iodide in 250 ml of tetrahydrofuran under a nitrogen atmosphere was added portionwise over ca. 5 min., 6.7 g (60 mmol) of potassium tert.-butoxide. The reaction temperature rose to 30°. After stirring at room temperature over night (16 hr.), the reaction was heated at reflux (oil bath) for 4.5 hr. to produce (Z)-1α,3β-pregna-5,17(20)-diene-1,3-diol (Tlc: EtOAc, showed starting material was consumed). On cooling to 50°, 60 ml of pyridine and 30 ml of acetic anhydride were added, and the reaction solution left stirring over night (18 hr.) and then heated at reflux for 2 hr. Acetylation was still incomplete (Tlc: 4:1, hexane--ethyl acetate showed mono and diacetates). Consequently, 100 mg of 4-dimethylaminopyridine was added, and heating at reflux was continued for 5 hr. Then, the reaction solution was diluted with 250 ml of 80% aqueous methanol (v/v) and, after cooling to room temperature, was extracted with 3×200 ml of hexane. The organic phases were washed in a countercurrent manner with 250 ml of 80% aq. methanol (v/v) and evaporated under reduced pressure to give 12.0 g of crude product. Chromatography on 500 g of silica gel prepared in hexane, and elution with 200 ml fractions of 8:1, hexane--ethyl acetate afforded, in fractions 7-11, 6.8 g of impure product and, in fractions 12-17, 4.2 g of pure product. The combined fractions 7-11, on rechromatography, gave 6.2 g of pure product. Thus, a total of 10.4 g (87%) of pure 1α,3β-diacetyloxypregna-5,17(20)-diene as an amorphous solid, was obtained as a 95:5 mixture of Z and E isomers, respectively. An analytical sample of (Z)-1α,3β-diacetyloxypregna-5,17(20)-diene, obtained by two recrystallizations from methanol, had mp 90°-91°.

후처리

  1. additionwas added portionwise over ca. 5 min.
  2. customrose to 30°
  3. temperaturethe reaction was heated
  4. temperatureat reflux (oil bath) for 4.5 hr

출처 및 근거

ORD 기록
ord-833eb91aae3544b09ad4aee85bd638df
출처 데이터셋
uspto-grants-1982_01
특허 번호
US04310467

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