Hydrochloric Acid → HCID 10783379, compound

HRID 2256865Notes

Reaction equation

HRID 2256865 reaction equation
[CH2:1](OCC)C.C(N(CC)CC)C.Cl[Si](C)(C)C.[CH:18]([C:21]1[C@H:26]2[C@H:27]3[C@H:36]([CH2:37][CH2:38][C@:24]2([CH3:25])[C:23](=[O:41])[CH:22]=1)[C:35]1[CH:34]=[CH:33][C:32]([O:39][CH3:40])=[CH:31][C:30]=1[CH2:29][CH2:28]3)([CH3:20])[CH3:19].[Cl-].[NH4+].Cl>O1CCCC1>[CH:18]([C@:21]1([CH3:1])[C@H:26]2[C@H:27]3[C@H:36]([CH2:37][CH2:38][C@:24]2([CH3:25])[C:23](=[O:41])[CH2:22]1)[C:35]1[CH:34]=[CH:33][C:32]([O:39][CH3:40])=[CH:31][C:30]=1[CH2:29][CH2:28]3)([CH3:20])[CH3:19]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 10853457HCID 10853457, compound

Product 1

HCID 10783379HCID 10783379, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of lithium dimethyl cuprate (0.61 mmol) in dry diethyl ether (1.5 ml) [prepared at 0° C. from copper(I) iodide (118 mg; 0.61 mmol) and methyl lithium (0.8 ml; 1.6M; 1.28 mmol)] was cooled to -78° C. Triethylamine (0.1 ml; 0.72 mmol) and chlorotrimethylsilane (0.1 ml; 0.79 mmol) were sequentially added. Stirring at -78° C. was maintained for 5 min., before a solution of the isopropyl eneone (10) (100 mg; 0.31 mmol) in dry tetrahydrofuran (3 ml) was added dropwise. The reaction was stirred for a further 30 min. at 0° C. Saturated aqueous ammonium chloride and dilute HCl were added. To allow complete hydrolysis of the enol silyl ether, the mixture was stirred at 20° C. for 15 min. The residue upon work-up (ethyl acetate) (97 mg) was chromatographed on silica gel (10 g), and eluting with ethyl acetate-toluene (1:49) gives 15β-isopropyl-3-methoxy-15β-methylestra-1,3,5(10)-trien-17-one (11) (92 mg; 86%), m.p. 113°-115° C. (from diisopropyl ether); [α]D +87° (c 0.9); υmax 1724 cm-1 (CO); δH (C6D6), 0.68 (6H, d, J 6.0 Hz, 15α-CHMe2), 0.87 (3H, s, 15β-Me), 0.98 (3H, s, 13β-Me), 1.62 obsc (1H, q, J 6.0 Hz, 15α-CHMe2), 1.95 and 2.15 (each 1H, d, J 19.1 Hz, 16α- and 16β-H), 2.68 (2H, m, 6-H2), 3.44 (3H, s, 3-OMe), 6.70 (1H, d, J 2.6 Hz, 4-H), 6.79 (1H, dd, J 8.8 and 2.6 Hz, 2-H), and 7.09 (1H, d, J 8.8 Hz, 1-H); δH (CDCl3) 0.87 and 0.89 (each 3H, d, J 6.7 Hz, 15α-CHMe2), 1.13 (3H, s, 13β-Me), 1.32 (3H, s, 15β-Me), 2.23 obsc. (2H, d, J 18.7 Hz, 16α- and 16β-H), 2.87 (3H, m, 6-H2), 3.77 (3H, s, 3-OMe), 6.68 (1H, d, J 2.8 Hz, 4-H), 6.75 (1H, dd, J 8.8 and 2.8 Hz, 2-H), and 7.20 (1H, d, J 8.8 Hz, 1-H); δC 17.8 (C-18), 18.4 and 18.8 (15α-CHMe2), 23.0 (C-11), 26.1 (C-7), 27.8 (15β-Me), 30.0 (C-8), 34.5 (C-12), 36.9 (15α-CHMe2), 37.7 (C-6), 41.5 (C-15), 44.6 (C-9), 45.0 (C-16), 49.9 (C-13), 51.6 (C-14), 55.2 (3-OMe), 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 220.3 (C-17) (Found: C, 81.2; H, 9.6%; M+, 340. C23H32O2 requires C, 81.1; H, 9.5%; M, 340).

Workup

  1. additionwas added dropwise
  2. stirringThe reaction was stirred for a further 30 min. at 0° C
  3. stirringthe mixture was stirred at 20° C. for 15 min
  4. customThe residue upon work-up (ethyl acetate) (97 mg) was chromatographed on silica gel (10 g)
  5. washeluting with ethyl acetate-toluene (1:49)

Sources & evidence

ORD record
ord-26d694b5bfc843daa485746c3d278dc9
Source dataset
uspto-grants-1997_08
Patent number
US05656622

Reaction notes

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