Ammonia → 15beta-Ethyl-3-methoxy-15beta-methylestra-1,3,5(10)-trien-17-one

HRID 1081982Notes

Reaction equation

C[Mg]I.[CH2:4](OCC)C.[CH2:9]([C:11]1[C@H:16]2[C@H:17]3[C@H:26]([CH2:27][CH2:28][C@:14]2([CH3:15])[C:13](=[O:31])[CH:12]=1)[C:25]1[CH:24]=[CH:23][C:22]([O:29][CH3:30])=[CH:21][C:20]=1[CH2:19][CH2:18]3)[CH3:10].[Cl-].[NH4+].N>O1CCCC1.[Cu]I>[CH2:9]([C@:11]1([CH3:4])[C@H:16]2[C@H:17]3[C@H:26]([CH2:27][CH2:28][C@:14]2([CH3:15])[C:13](=[O:31])[CH2:12]1)[C:25]1[CH:24]=[CH:23][C:22]([O:29][CH3:30])=[CH:21][C:20]=1[CH2:19][CH2:18]3)[CH3:10]

Participants

Conditions

Temperature: 20 °C

Procedure

A solution of methylmagnesium iodide (2.5 mmol) in dry diethyl ether (2.5 ml) [prepared at 20° C. from magnesium (60 mg; 2.5 mmol) and methyl iodide (0.16 ml; 2.5 mmol)] was cooled to 0° C. Copper(I) iodide (46 mg; 0.24 mmol) was added. After 5 min. at 0° C., a solution of the 15-ethyl-Δ15 -17-ketone (7) (150 mg; 0.48 mmol) in dry tetrahydrofuran (3 ml) was added. The mixture was stirred at 20° C. for 15 min. Saturated aqueous ammonium chloride and aqueous ammonia were added and the residue upon work-up (ethyl acetate) (150 mg; 96%) was crystallized from chloroform to give the 15α-ethyl-3-methoxy-15β-methylestra-1,3,5 (10)-trien-17-one (8) (127 mg; 81%); m.p. 110°-113° C. (from chloroform-methanol); [α]D +90° (c 1.0); νmax 1724 cm-1 (CO); δH 0.89 (3H, t, J 7.4 Hz, 15α-CH2CH3), 1.12 (3H, s, 13β-Me), 1.25 (3H, s, 15β-Me), 1.36 and 1.76 (each 2H, degen. dq, J 14.8 and 3×7.4 Hz, 15α-CH2CH3), 2.18 and 2.44 (each 1H, d, J 19.4 Hz, 16α- and 16β-H), 2.88 (2H, m, 6-H2), 3.77 (3H, s, 3-OMe), 6.62 (1H, d, J 2.9 Hz, 4-H), 6.71 (1H, dd, J 8.6 and 2.9 Hz, 2-H), and 7.20 (1H, d, J 8.6 Hz, 1-H); δc 9.4 (C-152), 18.2 (C-18), 21.8 (C-151), 26.1 (C-11), 28.3 (C-7), 29.9 (C-6), 34.2 (C-12), 37.5 (C-8), 38.1 (15β-Me), 38.9 (C-15), 44.9 (C-9), 49.8 (C-16), 50.0 (C-13), 55.2 (3-OMe), 56.6 (C-14), 111.6 (C-2), 113.6 (C-4), 126.5 (C-1), 132.2 (C-10), 137.4 (C-5), 157.6 (C-3), and 220.4 (C-17) (Found: C, 81.2; H, 9.5%; M+, 326. C22H30O2 requires C, 80.9; H, 9.3%; M, 326).

Workup

customthe residue upon work-up (ethyl acetate) (150 mg; 96%) was crystallized from chloroform

Sources & evidence

ORD record: ord-a7fe13e92b5542f3802fb01174f69c1a
Source dataset: uspto-grants-1996_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05587496

Reaction notes

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