Estrone → HCID 22983884, compound

HRID 1263484Notes

Reaction equation

HRID 1263484 reaction equation
[CH3:1][C@@:2]12[C:18](=[O:19])[CH2:17][CH2:16][C@H:15]1[C@H:14]1[C@@H:5]([C:6]3[CH:7]=[CH:8][C:9]([OH:20])=[CH:10][C:11]=3[CH2:12][CH2:13]1)[CH2:4][CH2:3]2.[H-].[Na+].[H][H].[CH3:25][S:26][CH2:27]Cl>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)(Cl)Cl.O>[CH3:25][S:26][CH2:27][O:20][C:9]1[CH:8]=[CH:7][C:6]2[C@@H:5]3[C@H:14]([C@H:15]4[C@@:2]([CH2:3][CH2:4]3)([CH3:1])[C:18](=[O:19])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]=2[CH:10]=1

Participants

9

Reactant 4

HCID 5870EstroneHCID 16916Chloromethyl methyl sulfideHCID 24758Sodium hydrideHCID 178418361HCID 178418361, compound

Product 1

HCID 22983884HCID 22983884, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of estrone (2.0 g, 7.39 mmol) in anhydrous DMF under Ar (g), was added NaH (60% in oil, 0.26g, 11.0 mmol). After the evolution of hydrogen had ceased, the solution was cooled in an ice bath for the addition of CH3SCH2Cl (3.56 g, 36.9 mmol, 3.08 mL) and DMAP (0.09 g, 7.0 mmol). The solution was stirred in a cold room (4° C.) for 16 hours. The reaction was stopped with cold water, extracted with ethyl acetate, wash with water and brine, dry over MgSO4, filtered and concentrated under reduce pressure. The crude extract was purified by flash chromatography on silica gel column and eluted with EtOAc:hexanes (1:9), to give EM-1066 (0.7 g, 30%) as a white solide; Rf 0.5 (3:7 EtOAc/Hexanes); M.p.65° C.; [α]D26 +116.40 (c 1.06, CHCl3); IR (ν) 2919, 2864, 1735, 1604, 1577, 1497, 1448, 1375, 1282, 1255, 1211, 1151, 1051, 989, 885, 823, 787, 739,640-690, 579 cm−1; 1H NMR δ 2.24 (3H, s, CH3—S), 5.12 (2H, s, S—CH2—O), 7.21 (1H, d, J=2.8 Hz, 1′-CH), 6.76 (2H, dd, j1=2.8 Hz and J2=8.6 Hz, 2′-CH), 6.70 (1H, d, J=8.0 Hz, 4′-CH).

Workup

  1. extractionextracted with ethyl acetate
  2. washwash with water and brine
  3. dry with materialdry over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. extractionThe crude extract
  7. customwas purified by flash chromatography on silica gel column
  8. washeluted with EtOAc:hexanes (1:9)
  9. customto give EM-1066 (0.7 g, 30%) as a white solide

Sources & evidence

ORD record
ord-027a445147ce4836902e377d2184444a
Source dataset
uspto-grants-2003_04
Patent number
US06541463B1

Reaction notes

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