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tography (SiO2, hexane/MTBE=3:1, Rf =0.26) to yield alcohol 7
(4.02 g, 13.8 mmol, 97%) as colorless crystals. M.p. 1438C. [a]D20
reflux for 2 h. The solvent was removed in vacuum to give oxime 8
=
(324 mg, 1.01 mol, quant.) as colorless crystals. M.p. 1408C; [a]D20
=
+6.7 (CH2Cl2, 1 gLÀ1) (lit. mp.: 145–1468C. [a]D20 = +6.3 (CHCl3,
0.5 gLÀ1)).[21] 1H NMR (500 MHz, CDCl3): d=0.59 (s, 3H), 0.65 (ddd,
J=14.7, 10.6, 4.0 Hz, 1H), 0.74 (s, 3H), 0.79–0.90 (m, 2H), 0.95–1.01
(m, 2H), 1.04–1.24 (m, 10H), 1.28–1.40 (m, 2H), 1.42–1.50 (m, 2H),
1.53–1.64 (m, 5H), 1.72–1.82 (m, 2H), 3.48 (dd, J=10.5, 7.6 Hz, 1H),
3.66 ppm (dd, J=10.5, 6.8 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3):
d=12.24 (CH3), 12.63 (CH3), 20.54 (CH2), 22.19 (CH2), 24.45 (CH2),
25.28 (CH2), 26.82 (CH2), 29.06 (CH2), 29.07 (CH2), 32.25 (CH2), 35.27
(CH), 36.35 (C), 38.74 (CH2), 38.95 (CH2), 41.95 (C), 47.12 (CH), 53.15
(CH), 55.07 (CH), 56.16 (CH), 64.70 ppm (CH2); IR (ATR): n˜ =3378
(m), 2969 (m), 2937 (s), 2913 (s), 2868 (s), 2853 (s), 1469 (m), 1447
(m), 1002 cmÀ1 (s); MS (EI, 70 eV): m/z (%): 290 (38) [M+], 275 (42),
257 (28), 235 (9), 232 (23), 218 (79), 217 (100), 203 (14), 189 (7), 180
(10), 162 (20), 149 (55), 135 (19), 121 (22), 109 (32), 95 (35), 81 (36),
67 (30), 55 (30); HRMS (EI): calcd 290.2604 (for C19H34O); found:
290.2607 [M+]; 290.49 (C20H34O).
+17.0 (CH2Cl2, 1 gLÀ1); H NMR (500 MHz, CDCl3): d=0.72 (s, 3H),
0.74–0.79 (m, 1H), 0.83–0.89 (m, 1H), 0.91–0.97 (m, 1H), 0.99–1.05
(m, 1H), 1.14–1.26 (m, 6H), 1.27–1.43 (m, 6H), 1.46–1.50 (m, 1H),
1.57 (dq, J=13.4, 3.7 Hz, 1H), 1.62–1.71 (m, 3H), 1.78–1.85 (m, 2H),
1.91–1.97 (m, 1H), 2.42 (dt, J=12.1, 3.1 Hz, 1H), 2.82 (brs, 1H),
3.55–3.62 (m, 2H), 7.36 (s, 1H), 8.46 ppm (brs, 1H); 13C{1H} NMR
(125 MHz, CDCl3): d=12.21 (CH3), 21.21 (CH2), 22.09 (CH2), 24.47
(CH2), 24.77 (CH2), 26.74 (CH2), 28.74 (CH2), 28.97 (CH2), 32.05 (CH2),
35.90 (CH2), 36.30 (C), 36.74 (CH), 38.65 (CH2), 46.72 (CH), 49.71 (C),
52.30 (CH), 54.86 (CH), 56.33 (CH), 63.97 (CH2), 153.96 ppm (CH); IR
(ATR): n˜ =3320 (m), 2919 (s), 2852 (s), 1446 (m), 1034 (m),
1012 cmÀ1 (m); MS (ESI+): m/z: 320 [M+H+], 342 [M+Na+]; HRMS
(ESI): m/z: calcd 342.2404 (for C20H33NNaO2); found: 342.2413
[M+Na+]; 319.49 (C20H33NO2).
1
5a-Androstan-17b-carboxaldehyde (9)
Barton reaction of alcohol 7
M.p. 1068C; [a]D20 =12.4 (CH2Cl2, 2.7 gLÀ1); 1H NMR (500 MHz,
CDCl3): d=0.68–0.77 (m, 1H), 0.73 (s, 3H), 0.78 (s, 3H), 0.85–0.94
(m, 2H), 1.00–1.06 (m, 1H), 1.08–1.15 (m, 1H), 1.18–1.27 (m, 7H),
1.35–1.42 (m, 3H), 1.46–1.52 (m, 1H), 1.59 (ddd, J=13.5, 7.0,
3.8 Hz, 1H), 1.64–1.75 (m, 5H), 1.96 (dt, J=12.3, 3.3 Hz, 1H), 2.05–
2.14 (m, 1H), 2.26–2.29 (m, 1H), 9.67 ppm (d, J=2.1 Hz, 1H);
13C{1H} NMR (125 MHz, CDCl3): d=12.21 (CH3), 13.96 (CH3), 20.29
(CH2), 20.97 (CH2), 22.12 (CH2), 24.79 (CH2), 26.74 (CH2), 28.91 (CH2),
28.98 (CH2), 32.11 (CH2), 35.05 (CH), 36.32 (C), 38.57 (CH2), 38.67
(CH2), 44.96 (C), 47.00 (CH), 54.72 (CH), 56.39 (CH), 63.00 (CH),
A solution of alcohol 7 (500 mg, 1.72 mmol) in CHCl3 (17 mL) was
treated with tert-butyl nitrite (2.00 mL, 1.77 g, 17.2 mmol) and the
mixture was stirred for 30 min in the dark. All volatile materials
were evaporated and the crude solid was dried in high vacuum for
3 h. The residue was dissolved in anhydrous acetone (350 mL,
22 molLÀ1). Portions of 80 mL each were placed successively in
a bubble column reactor with an inner 150 W Hg-lamp and an
outer cooling jacket and were irradiated for 20 min, while a laminar
stream of N2 was passed slowly through the solution and the tem-
perature was maintained at 208C. The colorless precipitate was fil-
tered off to give a first portion of nitroso compound 3 (176 mg,
0.55 mmol, 32%). The combined filtrates were concentrated and
submitted to column chromatography (SiO2, hexane/MTBE=3:1).
In the first fraction, aldehyde 9 (35 mg, 0.12 mmol, 7%; Rf =0.58)
was obtained as a colorless oil. Secondly, starting material 7
(143 mg, 0.49 mmol, 29%; Rf =0.26) was recovered. The third frac-
tion contained oxime 8 (30 mg, 0.09 mmol, 5%; Rf =0.14) as color-
less crystals. Finally, a second portion of nitroso compound 3
(148 mg, 0.46 mmol, 27%; Rf =0.08) was received in the fourth frac-
tion.
205.24 ppm (CH); IR (ATR): n=2923 (s), 2849 (m), 1718 (vs),
˜
1446 cmÀ1 (m); MS (EI, 70 eV): m/z (%): 288 (10) [M+], 273 (8), 255
(8), 243 (5), 231 (5), 217 (10), 203 (5), 189 (3), 175 (8), 162 (7), 149
(22), 135 (43), 133 (16), 119 (16), 109 (44), 106 (10), 95 (70), 91 (51),
81 (81), 77 (31), 67 (100), 53 ppm (28); HRMS (EI): calcd 288.2448
(for C20H32O); found: 288.2453 [M+]; 288.48 (C20H32O).
17b-(Hydroxymethyl)-5a-androstano-18-nitrile (10)
2-Chloro-1-methylpyridinium iodide (2.15 g, 8.43 mmol) was added
to a solution of oxime 8 (2.07 g, 6.48 mmol) in CH2Cl2 (40 mL).
After stirring the mixture for 10 min, NEt3 (1.17 mL, 853 mg,
8.43 mmol) was added and the resulting mixture was heated to
408C for 24 h. After cooling to ambient temperature, the solvent
was evaporated. The residue was column chromatographed (SiO2,
hexane/EtOAc=2:1, Rf =0.37) to furnish nitrile 10 (1.24 g,
4.11 mmol, 63%) as colorless crystals. M.p. 1778C; [a]2D0 = +10
(CH2Cl2, 1 gLÀ1); 1H NMR (500 MHz, CDCl3): d=0.75 (ddd, J=12.1,
J=10.7, J=3.7 Hz, 1H), 0.81 (s, 3H), 0.87 (td, J=13.3, J=4.7 Hz,
1H), 0.92–0.98 (m, 1H), 0.99–1.06 (m, 1H), 1.18–1.35 (m, 7H), 1.39–
1.51 (m, 5H), 1.59 (qd, J=10.9, 4.0 Hz, 1H), 1.64–1.69 (m, 2H),
1.71–1.91 (m, 5H), 1.94–2.02 (m, 1H), 2.37 (dt, J=12.9, 3.2 Hz, 1H),
3.78 (dd, J=10.8, 6.2 Hz, 1H), 3.87 ppm (dd, J=10.8, 8.3 Hz, 1H);
13C{1H} NMR (125 MHz, CDCl3): d=12.18 (CH3), 22.01 (CH2), 22.18
(CH2), 24.85 (CH2), 25.43 (CH2), 26.64 (CH2), 28.48 (CH2), 28.84 (CH2),
31.44 (CH2), 34.61 (CH2), 36.21 (C), 38.21 (CH), 38.67 (CH2), 46.75
(CH), 49.91 (CH), 50.04 (C), 53.78 (CH), 55.62 (CH), 64.43 (CH2),
121.27 ppm (C); IR (ATR): n˜ =3472 (m), 2917 (s), 2851 (s), 2224 (w),
1445 (m), 1381 (s), 1042 (m), 1030 (m), 1015 (m), 1003 cmÀ1 (m);
MS (EI): m/z (%): 301 (40) [M+], 286 (42), 259 (7), 245 (27), 244 (61),
217 (9), 216 (7), 199 (4), 165 (5), 147 (6), 133 (7), 110 (100), 95 (26),
81 (23), 67 (19), 55 (17); HRMS (ESI+): calcd 324.2298 (for
C20H31NNaO); found: 324.2309 [M+Na+]; 301.47 (C20H31NO).
17b-(Hydroxymethyl)-18-nitroso-5a-androstane (3)
M.p. 1518C; [a]D20 = +40.0 (CH2Cl2, 1 gLÀ1); 1H NMR (500 MHz,
CDCl3): d=0.70–0.75 (m, 1H), 0.79 (s, 3H), 0.83–0.99 (m, 4H), 1.01–
1.05 (m, 1H), 1.17–1.25 (m, 7H), 1.30–1.48 (m, 4H), 1.53–1.59 (m,
2H), 1.65–1.79 (m, 4H), 1.88–1.95 (m, 1H), 2.28 (dt, J=13.7, 2.6 Hz,
1H), 3.39 (d, J=13.9 Hz, 1H), 3.66–3.71 (m, 2H), 3.76–3.79 (m, 1H),
5.46 ppm (d, J=13.9 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3): d=
12.44 (CH3), 20.74 (CH2), 22.04 (CH2), 23.50 (CH2), 23.76 (CH2), 26.71
(CH2), 28.80 (CH2), 28.86 (CH2), 31.76 (CH2), 34.29 (CH2), 35.66 (CH),
36.33 (C), 38.82 (CH2), 46.85 (CH), 47.21 (C), 52.86 (CH), 54.32 (CH2),
54.62 (CH), 57.77 (CH), 64.02 ppm (CH2); IR (ATR): n˜ =3384 (m),
2913 (s), 2850 (s), 1465 (m), 1445 (m), 1381 (m), 1227 (m), 1198 (m),
1177 (s), 1050 (m), 1026 (m), 1009 cmÀ1 (m); MS (ESI+): m/z: 320
[M+H+], 342 [M+Na+]; HRMS (ESI+): calcd 342.2404 (for
C20H33NNaO2); found: 342.2410 [M+Na+]; 319.49 (C20H33NO2).
17b-(Hydroxymethyl)-18-oximino-5a-androstane (8)
Small amounts were obtained from the Barton reaction. It was also
prepared by the following isomerization: A solution of nitroso
compound 3 (324 mg, 1.01 mmol) in iPrOH (50 mL) was heated to
Chem. Eur. J. 2015, 21, 12501 – 12508
12505
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