Ethyl Acetate → 3-Methoxy-15,15-dimethylestra-1,3,5(10)-trien-17-one

HRID 1081979Notes

Reaction equation

HRID 1081979 reaction equation
C[Li].[CH3:3][O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C:14](=[O:23])[CH:13]=[C:12]4[CH3:24])[CH2:9][CH2:8][C:7]=2[CH:6]=1.[Cl-].[NH4+].[C:27](OCC)(=O)C>C(OCC)C.O1CCCC1.[Cu]I>[CH3:3][O:4][C:5]1[CH:22]=[CH:21][C:20]2[C@@H:19]3[C@H:10]([C@H:11]4[C@@:15]([CH2:17][CH2:18]3)([CH3:16])[C:14](=[O:23])[CH2:13][C:12]4([CH3:27])[CH3:24])[CH2:9][CH2:8][C:7]=2[CH:6]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 106853783-Methoxy-15-methylestra-1,3,5(10),15,tetraen-17-oneHCID 178418348HCID 178418348, compound

Product 1

HCID 108050863-Methoxy-15,15-dimethylestra-1,3,5(10)-trien-17-oneYield 70%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of lithium dimethylcuprate (0.79 mmol) in dry diethyl ether (2 ml) [conventionally prepared at 0° C. from copper(I) iodide (150 mg; 0.79 mmol) and methyl lithium (1.3 ml; 1.6M; 2.08 mmol)] at -78° C., boron trifluor-ide-diethyl ether complex (0.1 ml; 0.80 mmol) was added, followed by the 15-methyl-Δ15 -17-ketone (3) (163 mg; 0.55 mmol) in dry tetrahydrofuran (2 ml). After 30 min., saturated aqueous ammonium chloride was added. The standard work-up (ethyl acetate) gave a crystalline residue, chromatography of which on silica gel (5 g), eluting with ethyl acetate-toluene (1:19) gave the 15,15-dimethylketone (4) (146 mg; 70%), m.p. 145°-148° C. (from ethyl acetate-methanol); [α]D +75° (C 1.0); νmax 1727 cm-1 (CO); δH 1.10 (3H, s, --β-Me), 1.28 and 1.29 (each 3H, s, 15α- and 15β-Me), 1.84 (1H, d, J 10.9 Hz, 14α-H), 2.09 and 2.61 (each 1H, d, J 19.4 Hz, 16α- and 16β-H), 2.93 (2H, m, 6-H2), 3.78 (3H, s, 3-OMe), 6.63 (1H, d, J 2.7 Hz, 4-H), 6.70 (1H, dd, J 8.6 and 2.7 Hz, 2-H), and 7.21 (1H, d, J 8.6 Hz, 1-H); δc 17.8 (C-18), 24.5 (15-Me), 26.0 (C-11), 28.2 (C-7), 29.8 (C-6), 34.2 (C-12), 34.6 (15-Me), 35.5 (C-15), 37.5 (C-8), 44.9 (C-9), 50.2 (C-13), 53.6 (C-16), 55.2 (3-OMe), 58.4 (C-14), 111.6 (C-2), 113.6 (C-4), 126.4 (C-1), 132.2 (C-10), 137.4 (C-5), 157.6 (C-3), and 221.4 (C-17) (Found: C, 80.5; H, 8.8%; M+, 312. C21H28O2 requires C, 80.7; H, 9.0%; M, 312).

Workup

  1. additionboron trifluor-ide-diethyl ether complex (0.1 ml; 0.80 mmol) was added
  2. washeluting with ethyl acetate-toluene (1:19)

Sources & evidence

ORD record
ord-578137b3b38546449a1d1a8d02652761
Source dataset
uspto-grants-1996_12
Patent number
US05587496

Reaction notes

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