Chlorotrimethylsilane → HCID 10853457, compound

HRID 2256864Notes

Reaction equation

HRID 2256864 reaction equation
[CH:1]([C@H:4]1[C@H:9]2[C@H:10]3[C@H:19]([CH2:20][CH2:21][C@:7]2([CH3:8])[C:6](=[O:24])[CH2:5]1)[C:18]1[CH:17]=[CH:16][C:15]([O:22][CH3:23])=[CH:14][C:13]=1[CH2:12][CH2:11]3)([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].Cl[Si](C)(C)C.[Cl-].[NH4+]>O1CCCC1.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[CH:1]([C:4]1[C@H:9]2[C@H:10]3[C@H:19]([CH2:20][CH2:21][C@:7]2([CH3:8])[C:6](=[O:24])[CH:5]=1)[C:18]1[CH:17]=[CH:16][C:15]([O:22][CH3:23])=[CH:14][C:13]=1[CH2:12][CH2:11]3)([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 10806068HCID 10806068, compound

Product 1

HCID 10853457HCID 10853457, compoundYield 81.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the 15β-isopropyl ketone (9) (210 mg; 0.64 mmol) in dry tetrahydrofuran (10 ml) was added to a solution of lithium diisopropylamide (3.2 mmol) [prepared at 0° C. from diisopropylamine (0.9 ml; 6.35 mmol) in tetrahydrofuran (2 ml) and butyl lithium (1.9 ml; 3.04 mmol)] at -78° C. After 30 min. at this temperature, chlorotrimethylsilane (1 ml; 7.88 mmol) was added. The mixture was allowed to warm to 0° C. over 20 min. Saturated aqueous ammonium chloride was added and the residue upon work-up (ethyl acetate). (242 mg) was dissolved in dry acetonitrile (20 ml). Palladium(II) acetate (140 mg; 0.62 mmol) was added and the mixture was heated to refluxing temperature for 20 min. The solution was cooled to 20° C., filtered and evaporated. The residue (230 mg) was chromatographed on silica gel (23 g), and eluting with ethyl acetate-toluene (1:19) gives 15-isopropyl-3-methoxyestra-1,3,5(10),15-tetraen-17-one (10) (170 mg; 81% from 9), m.p. 113°-116° C. (from chloroform-methanol); [α]D -18° (c 1.0); υmax 1690 cm-1 (CO); δH 1.10 (3H, s, 13β-Me), 1.16 and 1.22 (each 3H, d, J 6.6 Hz, 15-CHMe2), 2.57 (1H, dd, J 11.2 and 2.7 Hz, 14α-H), 2.92 (2H, m, 6-H2), 3.79 (3H, s, 3-OMe), 5.80 (1H, dd, J 2.7 and 1.2 Hz, 16-H), 6.65 (1H, d, J 2.7 Hz, 4-H), 6.74 (1H, dd, J 8.6 and 2.7 Hz, 2-H), and 7.24 (1H, d, J 8.6 Hz, 1-H); δC 21.1 (C-18), 21.6 and 21.7 (15-CHMe2), 25.6 (C-11), 28.1 (C-7), 29.1 (C-6), 29.7 (C-8), 30.8 (15-CHMe2), 37.4 (C-12), 45.4 (C-9), 52.6 (C-13), 55.2 (3-OMe), 56.3 (C-14), 111.6 (C-2), 113.6 (C-3), 123.9 (C-16), 126.3 (C-1), 132.2 (C-10), 137.2 (C-5), 157.7 (C-3), 185.7 (C-15), and 212.4 (C-17) (Found: C, 81.6; H, 8.9%; M+, 324. C22H28O2 requires C, 81.4; H, 8.7%; M, 324).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto refluxing temperature for 20 min
  3. temperatureThe solution was cooled to 20° C.
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue (230 mg) was chromatographed on silica gel (23 g)
  7. washeluting with ethyl acetate-toluene (1:19)

Sources & evidence

ORD record
ord-62b07565af8b45578349f87e8300b41a
Source dataset
uspto-grants-1997_08
Patent number
US05656622

Reaction notes

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