Lawesson's reagent → HCID 11438051, compound

HRID 1637576Notes

Reaction equation

HRID 1637576 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@H:9]4[C@@:13]([CH2:15][CH2:16]3)([CH3:14])[C:12](=O)[CH2:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:31])=CC=1>O1CCCC1.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@H:9]4[C@@:13]([CH2:15][CH2:16]3)([CH3:14])[C:12](=[S:31])[CH2:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1

Participants

5

Reactant 2

HCID 87949Lawesson's reagent3×HCID 92895(+)-Estrone 3-methyl ether

Product 1

HCID 11438051HCID 11438051, compoundYield 109.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Estrone methyl ether (2, 17.64 g, 62.2 mmol) was dissolved in 500 mL of dry tetrahydrofuran (THF) and a first portion of Lawesson's reagent (13 g, 32 mmol) was added. The reaction mixture containing suspended solid was heated to reflux for 18 h when all solids dissolved and the solution became salmon red. A second portion of Lawesson's reagent (13 g, 32 mmol) was added and heating continued at reflux temperature for another 18 h. Similarly, a third portion of Lawesson's reagent (13 g, 32 mmol) was added; and after being heated for 18 h, the reaction mixture was cooled and the THF evaporated to give a thick slurry. The slurry was dissolved in a minimum amount of CH2Cl2 and passed through a pad of silica gel to remove a polar by-product of Lawesson's reagent. The eluent was concentrated to afford a bright orange solid which was further purified by column chromatography on silica gel with EtOAc-Hexanes (1:3) as eluent to afford a bright orange solid product (10.5 g, 35 mmol) in 56% yield as the first fraction and then starting material (4 g, 14.0 mmol) in 23% recovery. Crude thione 3 can be further purified by crystallizing from boiling EtOAc, although after column purification it is pure enough for subsequent reactions. 1H NMR (250 MHz, CDCl3) δ 0.94 (s, 3, C-S 8 CH3), 3.78 (s, 3, --OCH3), 6.64-6.75 (m, 2, ArH), 7.22 (d, J=10 Hz, 1 ArH); 13C NMR (250 MHz, CDCl3) δ 273.3 (C=S).

Workup

  1. additionThe reaction mixture containing
  2. temperaturewas heated
  3. temperatureto reflux for 18 h when all solids
  4. dissolutiondissolved
  5. temperatureheating
  6. temperatureat reflux temperature for another 18 h
  7. temperatureand after being heated for 18 h
  8. temperaturethe reaction mixture was cooled
  9. customthe THF evaporated
  10. customto give a thick slurry
  11. customto remove a polar by-product of Lawesson's reagent
  12. concentrationThe eluent was concentrated
  13. customto afford a bright orange solid which
  14. customwas further purified by column chromatography on silica gel with EtOAc-Hexanes (1:3) as eluent

Sources & evidence

ORD record
ord-3c8995e1882845118b82b7240bdf06c0
Source dataset
uspto-grants-2000_03
Patent number
US06043235

Reaction notes

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