On Steroids
383
5-Brom o-3β-h ydroxy-6β,19-epoxy-5α-pregn an -20-on e (4)
Com poun d 3 (1.0 g, 2.2 m m ol) was dissolved in m eth an ol (100 m l) an d potassium carbon -
ate (1.0 g, 7.2 m m ol) in water (20 m l) was added un der stirrin g. Th e course of th e reaction
was followed by TLC. After 30 m in , th e m ixture was evaporated to h alf of its volum e, th e
product was extracted with eth er, wash ed with water, dried an d evaporated un der reduced
pressure. Crystallization from m eth an ol gave 850 m g (93%) of com poun d 4, m .p. 183–185 °C,
[α ]2D0 +60 (c 1.1); ref.2 gives m .p. 179–180 °C, [α ]2D0 +61. IR: 3 625 (OH); 1 709 (C=O); 1 164,
1 097, 1 054, 909 (C–O–C). 1H NMR: 0.66 s, 3 H (3 × H-18); 2.09 s, 3 H (3 × H-21); 2.54 t, 1 H,
J = 8 (H-17α); 3.92 d an d 4.08 d, 2 H, AB system , J = 10.5 (2 × H-19); 4.08 d, 1 H, J = 7.5
(H-6α); 4.05–4.23 m , 1 H, W1/2 = 22 (H-3α). EI MS, m/e: 413, 411 (M + H)+; 393, 395 (M+
–
H2O). HR MS: for C21H31BrO3 calculated: 411.153481; foun d: 411.154100.
5-Brom o-3β-h ydroxy-20-oxo-6β,19-epoxy-5α-pregn an -21-yl Acetate (5)
Com poun d 4 (700 m g, 1.7 m m ol) in 5% m eth an olic ben zen e (21 m l) was stirred with boron
trifluoride eth erate (3.5 m l, 28.5 m m ol) for 20 m in at room tem perature. Lead tetraacetate
(1.49 g, 3.36 m m ol) was added an d th e stirrin g was con tin ued for 5 h . Th e m ixture was di-
luted with ben zen e an d worked up as usual. Evaporation gave 750 m g (94%) of oily product
5. Crystallization from aceton e–ligh t petroleum afforded crystalin e product as n eedles, m .p.
153–155 °C; ref.4 gives m .p. 153–155 °C. IR (KBr): 1 750 (C=O, acetate); 1 724, 1 703 (C=O,
keton e); 1 232, 1 020 (C–O, acetate); 1 056 (C–O, h ydroxyl); 594 (C–Br). 1H NMR: 0.65 s,
3 H (3 × H-18); 2.09 s, 3 H (CH3COO); 2.52 t, 1 H, J = 8 (H-17α); 3.65 d an d 3.92 d, 2 H,
J = 9 (2 × H-19); 4.08 d, 1 H, J = 6.5 (H-6α); 4.05–4.23 m , 1 H, W1/2 = 22 (H-3α); 4.71 d an d
4.45 d, J = 15 (2 × H-21). FAB MS, m/e: 471, 469 (M + H)+.
5-Brom o-3,20-dioxo-6β,19-epoxy-5α-pregn an -21-yl Acetate (6)
Acetate 5 (755 m g, 1.6 m m ol) in aceton e (37.7 m l) at 5 °C was treated with Jon es reagen t
un til a perm an en t oran ge colour persisted. Th e excess reagen t was destroyed by addin g
propan -2-ol. After filtration , th e solution was diluted with dich lorom eth an e an d worked up as
usual. Evaporation of th e solven t at room tem perature gave th e un stable keton 6 (600 m g,
80%). Crystallization from m eth an ol gave n eedles, m eltin g poin t 99 °C; ref.4 gives
m .p. 103–104 °C. As th is com poun d rapidly decom posed, it was used for th e n ext reaction
step with out furth er purification .
3,20-Dioxo-6β,19-epoxypregn -4-en -21-yl Acetate (7)
Brom oketon e 6 (600 m g, 1.28 m m ol) obtain ed in th e previous experim en t was m ixed with
sodium acetate (0.7 g, 8.5 m m ol) an d m eth an ol (20 m l), an d th e reaction m ixture was
h eated un der reflux un til TLC detected n o startin g m aterial (1 h ). Water was added an d th e
product was extracted with ch loroform , wash ed with water an d dried. Th e solven t was
evaporated under reduced pressure. Product (360 mg, 73%) on crystallization from acetone–heptane
afforded n eedles of com poun d 7, m .p. 190 °C; ref.2 gives m .p. 193–194 °C. IR: 1 754 (C=O,
acetate); 1 730, 1 711 (C=O, 20-keton e); 1 690, 1 679 (C=O, 3-keton e); 1 232, 1 029 (C–O,
acetate). 1H NMR: 0.76 s, 3 H (3 × H-18); 2.17 s, 3 H (CH3COO); 2.51 t, 1 H, J = 8 (H-17α);
3.51 d an d 4.20 d, 2 H, J = 8.2 (2 × H-19); 4.70 d, 1 H, J = 7 (H-6α); 4.50 an d 4.73, 2 d, AB
system , J = 16 (2 × H-21); 5.82 s, 1 H (H-4). FAB MS, m/e: 387 (M + H)+.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)