NITRILE OXIDE APPROACH TO THE SYNTHESIS OF 23-22-OXO STEROIDS
1581
1
24-H). IR spectrum, , cm : 3030 2800, 1745, 1710,
1680, 1645, 1485, 1455, 1380, 1260, 1210, 1190,
1145, 1045, 990.
1780, 1705, 1680, 1640, 1465, 1385, 1335, 1300,
1300, 1280, 1210, 1185, 1105, 1025, 1010, 980, 950,
935, 905, 870.
(20S)-22-Acetamino-6 -methoxy-3 ,5-cyclo-
26,27-bisnor-5 -cholest-22-en-24-one (XX). Acetyl
chloride, 0.4 ml, was added with stirring to a solution
of 94 mg of enaminoketone V in 20 ml of pyridine.
After 3 h, the mixture was diluted with water and
extracted with ether. The extract was dried over
sodium sulfate, and evaporated, and the residue was
applied to a column charged with silica gel. Elution
with toluene ethyl acetate mixtures (30:1, 20:1, and
(20S)-6 -Methoxy-3 ,5-cyclo-26,27-bisnor-5 -
cholest-23-en-22-one (XXII). b. Methanesulfonyl
chloride, 0.02 ml, was added to a solution of 47 mg
of compound XXX in 4 ml of pyridine. The mixture
was kept for 1.5 h at room temperature, diluted with
water, and extracted with ether. The extract was dried
over sodium sulfate and evaporated, and the residue
was applied to a column charged with silica gel.
Elution with toluene ethyl acetate mixtures (60:1,
40:1, and 20:1) gave 43 mg (95%) of enone XXII.
1
10:1) gave 97 mg (93%) of acetamide XX. H NMR
spectrum, , ppm: 0.76 s (3H, 18-Me), 1.04 s (3H,
19-Me), 1.19 d (3H, 21-Me, J = 6.5 Hz), 2.06 s
(3H, 25-Me), 2.78 m (1H, 6-H), 3.33 s (3H, OMe),
5.03 s (1H, 23-H), 4.98 5.18 br.s (1H, NH), 9.76
9.92 br.s (1H, NH). IR spectrum, , cm : 3050 2800,
1720, 1650, 1605, 1370, 1245, 1105, 1025, 1005, 975.
Enones XXII and XXIII. a. Sodium tetrahydrido-
borate, 132 mg, was added at room temperature to
a solution of 677 mg of compound XX in 20 ml of
a 1:1 ethyl acetate methanol mixture. When the
reaction was complete, the mixture was neutralized
with hydrochloric acid and extracted with ethyl
acetate. The extract was dried over sodium sulfate
and evaporated. The residue was dissolved in 40 ml
(20S)-20-[5-(Bromomethyl)-4,5-dihydroisoxazol-
3-yl]-6 -methoxy-3 ,5-cyclo-5 -pregnane (XXVIII).
Pyridine, 1 ml, and N-chlorosuccinimide, 200 mg,
were added to a solution of 1.2 g of 6 -methoxy-
3 ,5-cyclo-24-nor-5 -cholan-23-al oxime [15] in
60 ml of chloroform, and the mixture was stirred until
it became homogeneous. A mixture of 1 ml of tri-
ethylamine and 1 ml of chloroform was added over
a period of 30 min, and 3 ml of allyl bromide was
then added. When the reaction was complete, the
mixture was evaporated, and the residue was applied
to a column charged with silica gel. Elution with
cyclohexane ethyl acetate mixtures (40:1, 30:1, and
1
20:1) gave 1.07 g (67%) of bromomethylisoxazole
1
of dioxane, 4 ml of acetic acid and 0.8 ml of water XXVIII. H NMR spectrum, , ppm: 0.78 s (3H,
were added, and the mixture was kept for 8 h at 65
70 C. It was then evaporated, and the residue was
applied to a column charged with silica gel. The
column was eluted with hexane ethyl acetate mixtures
(60:1, 50:1, and 40:1). Two fractions were collected.
18-Me), 1.03 s (3H, 19-Me), 1.15 d and 1.17 d (3H,
21-Me, J = 7 Hz), 2.78 m (1H, 6-H), 3.32 s (3H,
1
OMe), 4.68 4.86 m (1H, 24-H). IR spectrum, , cm :
3050 2800, 1470, 1390, 1340, 1305, 1280, 1220,
1110, 1025, 1010, 980, 900, 870.
The first fraction contained 122 mg (20%) of
(20S)-6 -Methoxy-20-[5-methyl-4,5-dihydroiso-
xazol-3-yl]-3 ,5-cyclo-5 -pregnane (XXIX). Azo-
bis(isobutyronitrile), 200 mg, and tributylstannane,
3 ml, were added to a solution of 1.4 g of bromo-
methyl derivative XXVIII in 25 ml of benzene.
The mixture was refluxed for 2 h under argon and
evaporated, and the residue was subjected to column
chromatography on silica gel using cyclohexane ethyl
acetate mixtures (60:1, 40:1, and 20:1) as eluent.
(20R)-6 -methoxy-3 ,5-cyclo-26,27-bisnor-5 -
1
cholest-23-en-22-one (XXIII). H NMR spectrum, ,
ppm: 0.71 s (3H, 18-Me), 1.00 s (3H, 19-Me), 1.04 d
(3H, 21-Me, J = 7 Hz), 1.93 d (3H, 25-Me, J = 7 Hz),
2.76 m (1H, 6-H), 3.32 s (3H, OMe), 6.20 d.d (1H,
23-H, J1 = 16, J2 = 2 Hz), 6.82 6.98 m (1H, 24-H).
1
IR spectrum, , cm : 3070, 3050 2800, 1780,
1705, 1680, 1640, 1465, 1385, 1335, 1300, 1300,
1280, 1210, 1185, 1105, 1025, 1010, 980, 950, 935,
905, 870.
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Yield of XXIX 1.1 g (94%). H NMR spectrum, ,
ppm: 0.77 s (3H, 18-Me), 1.01 s (3H, 19-Me), 1.15 d
(3H, 25-Me, J = 7 Hz), 1.27 d and 1.29 d (3H, 21-Me,
J = 7 Hz), 2.38 2.54 m and 2.84 3.02 m (2H, 23-H),
2.78 m (1H, 6-H), 3.32 s (3H, OMe), 4.54 4.74 m
From the second fraction we isolated 216 mg
(36%) of (20S)-6 -methoxy-3 ,5-cyclo-26,27-bisnor-
1
5 -cholest-23-en-22-one (XXII). H NMR spectrum,
1
(1H, 24-H). IR spectrum, , cm : 3050 2800, 1465,
, ppm: 0.76 s (3H, 18-Me), 1.01 s (3H, 19-Me),
1.11 d (3H, 21-Me, J = 7 Hz), 1.91 d (3H, 25-Me,
J = 7 Hz), 2.76 m (1H, 6-H), 3.32 s (3H, OMe),
6.17 d.d (1H, 23-H, J1 = 16, J2 = 2 Hz), 6.82 6.98 m
1390, 1335, 1305, 1280, 1210, 1190, 1105, 1025,
980, 870, 765.
(20S)-24-Hydroxy-6 -methoxy-3 ,5-cyclo-26,27-
bisnor-5 -cholestan-22-one (XXX). Boric acid,
1
(1H, 24-H). IR spectrum, , cm : 3070, 3050 2800,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 11 2001