Formic Acid → 3-Deoxy-estrone

HRID 1263479Notes

Reaction equation

HRID 1263479 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](O)=[CH:10][C:11]=3[CH2:12][CH2:13]1)[CH2:4][CH2:3]2.FC(F)(F)C(OC(=O)C(F)(F)F)=O.CCN(CC)CC.C(O)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>N1C=CC=CC=1.[O-]S([O-])(=O)=O.[Cu+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][C@:2]12[CH2:3][CH2:4][C@H:5]3[C@@H:14]([CH2:13][CH2:12][C:11]4[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=43)[C@@H:15]1[CH2:16][CH2:17][C:18]2=[O:19]

Participants

9

Reactant 5

HCID 284Formic AcidHCID 5870EstroneHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 11776Triphenylphosphine

Product 1

HCID 58823-Deoxy-estroneYield 65.3%

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 167845palladium(II) acetateCatalystHCID 1049PyridineSolvent

Procedure

At 0° C., 1.0 g (3.7 mmol) of estrone (73) was dissolved in 50 mL of dry pyridine and 1.24 mL (7.4 mmol) of trifluoroacetic anhydride (Tf2O) was added slowly to the solution. After 1 h, the crude solution was poured into a cold aqueous solution of CuSO4 (1M) and the organic phase washed with the same solution until the blue color disappear. Next, the solution was extracted with EtOAc and the organic phase washed with water, and dried over MgSO4. After evaporation of the solvent, the crude estrone-triflate was dissolved in 50 mL of dry DMF. To the resulting mixture, we added 1.54 mL (11 mmol) of Et3N, 0.41 mL (11 mmol) of HCOOH, 0.143 mg (0.55 mmol) of PPh3, and 30.8 mg (0.14 mmol) of Pd(OAc)2. After 3 h at room temperature, the solution was quenched with aqueous HCl (5%) and extracted with CH2Cl2. The organic phase was washed with water, dried over MgSO4, and solvents evaporated to dryness. The crude compound was purified by flash chromatography with hexanes/EtOAc (9:1) as eluent to give 615 mg (65% two steps) of 1,3,5(10)-estratrien-17-one (74). White solid; IR ν (film): 1738 (C═O); 1H NMR (CDCl3) δ 0.94 (s, 3H, 18-CH3), 2.94 (m, 2H, 6-CH2), 7.16 (m, 3H, 1-CH, 2-CH, 3-CH), 7.32 (d, J=5.9 Hz, 1H, 4-CH); 13C NMR (CDCl3) δ 13.76 (C-18), 21.51 (C-15), 25.61 (C-11), 26.42 (C-7), 29.29 (C-6), 31.56 (C-12), 35.77 (C-16), 38.04 (C-8), 44.40 (C-9), 47.88 (C-13), 50.49 (C-14), 125.22 (C-3), 125.73 (C-2 and C-1), 128.98 (C-4), 136.37 (C-5), 139.62 (C-10), 220.63 (C-17).

Workup

  1. washthe organic phase washed with the same solution until the blue color
  2. extractionNext, the solution was extracted with EtOAc
  3. washthe organic phase washed with water
  4. dry with materialdried over MgSO4
  5. customAfter evaporation of the solvent
  6. dissolutionthe crude estrone-triflate was dissolved in 50 mL of dry DMF
  7. waitAfter 3 h at room temperature
  8. customthe solution was quenched with aqueous HCl (5%)
  9. extractionextracted with CH2Cl2
  10. washThe organic phase was washed with water
  11. dry with materialdried over MgSO4, and solvents
  12. customevaporated to dryness
  13. customThe crude compound was purified by flash chromatography with hexanes/EtOAc (9:1) as eluent

Sources & evidence

ORD record
ord-d7764cd864c3407ea6275fcdb30e9554
Source dataset
uspto-grants-2003_04
Patent number
US06541463B1

Reaction notes

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