Cerium(III) chloride → HCID 59243438, compound

HRID 1685480Notes

Reaction equation

HRID 1685480 reaction equation
[Cl-].[Ce+3].[Cl-].[Cl-].[C:5]1([Mg]Br)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:13]([C@@:20]12[CH2:33]/[C:32](=[CH:34]\[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)/[C:31](=[O:41])[CH2:30][C@H:29]1[CH2:28][CH2:27][C:26]1[CH:25]=[C:24]([C:42]([OH:44])=[O:43])[CH:23]=[CH:22][C:21]2=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([Mg]Br)C1C=CC=CC=1>O1CCCC1.O.CO>[CH2:13]([C@@:20]12[CH2:33]/[C:32](=[CH:34]\[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)/[C@:31]([OH:41])([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:30][C@H:29]1[CH2:28][CH2:27][C:26]1[CH:25]=[C:24]([C:42]([OH:44])=[O:43])[CH:23]=[CH:22][C:21]2=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 24636Cerium(III) chlorideHCID 59243437HCID 59243437, compoundHCID 178418255HCID 178418255, compoundHCID 178419663HCID 178419663, compound2×

Product 1

HCID 59243438HCID 59243438, compoundYield 81.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

Cerium (III) Chloride (5.00 g, 20.29 mmol) was mixed in tetrahydrofuran (50 mL) at 50° C. for 16 hours. The temperature of the reaction was internally monitored with a JKEM. The resulting white milky solution was cooled to −75 C and stirred vigorously. The cold slurry was charged with phenyl magnesium bromide (1.0 M in THF, 19.1 mmol) dropwise over 15 minutes with the temperature maintained below −70° C. The solution was kept at −73° C. for 15 minutes and a solution of (4bR,6E,8aR)-4b-benzyl-6-benzylidene-7-oxo-4b,5,6,7,8,8a,9,10-octahydrophenanthrene-2-carboxylic acid (3.5 g, 8.311 mmol) in tetrahydrofuran (40 mL) was added dropwise over 20 minutes maintaining the reaction temperature below −70° C. HPLC/MS was obtained and indicated remaining starting material. The reaction was mixed for an additional 3 hours and an HPLC/MS was obtained and starting material remained. An additional 2 mL of benzyl magnesium bromide solution (2.0 mmol) was added over 10 minutes and an HPLC/MS obtained. An additional 1 mL of benzyl magnesium bromide solution (1.0 mmol) was added over 10 minutes and an HPLC/MS obtained. The solution was mixed for 30 minutes at −73° C. and allowed to warm to 10° C. and then cooled to 0° C. The reaction was quenched by the addition of saturated aqueous KHSO4 dropwise maintaining the temperature below 10° C. A total of 50 ml of the saturated solution was added. Solids formed in the solution and were removed by vacuum filtratration. The filter cake was washed with tetrahydrofuran (40 mL) and water (40 mL). Ethyl acetate (100 mL) was added and the layers separated. The organic layer was washed with saturated ammonium chloride (100 mL), dried over sodium sulfate, and solvent removed at reduced pressure. The aqueous layer was checked by HPLC/MS and did not contain any product. The residue was taken up in methanol (15 ml) and water added. The solution became milky and eventually a precipitate formed. Small amounts of methanol and water were added to improve the quality and quantity of precipitate. The solids were collected by vacuum filtration and air dried for about 2 hours. 3.4 grams of the title compound as a light yellow solid was obtained in 81% yield. 1H NMR (400 MHz, DMSO-d6) d ppm 12.65 (1H, s), 7.44-7.56 (7H, m), 7.34-7.39 (2H, m), 7.30 (2H, t, J=7.7 Hz), 7.12-7.22 (2H, m), 6.78 (1H, t, J=7.4 Hz), 6.50 (2H, t, J=7.8 Hz), 6.12 (1H, d, J=8.3 Hz), 5.86 (2H, d, J=7.3 Hz), 5.44 (1H, s), 3.61 (1H, d, J=14.2 Hz), 2.96 (1H, dd, J=17.6, 7.9 Hz), 2.80-2.91 (1H, m), 2.66-2.74 (1H, m), 2.50-2.65 (2H, m), 2.08 (1H, t, J=13.3 Hz), 1.82-1.93 (1H, m, J=13.2 Hz), 1.75-1.82 (1H, m), 1.59-1.74 (2H, m); LC/MS, tr=3.77 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50° C.).

Workup

  1. temperatureThe resulting white milky solution was cooled to −75 C
  2. temperaturemaintained below −70° C
  3. temperaturemaintaining the reaction temperature below −70° C
  4. customHPLC/MS was obtained
  5. additionThe reaction was mixed for an additional 3 hours
  6. customan HPLC/MS was obtained
  7. customan HPLC/MS obtained
  8. customan HPLC/MS obtained
  9. additionThe solution was mixed for 30 minutes at −73° C.
  10. temperaturecooled to 0° C
  11. customThe reaction was quenched by the addition of saturated aqueous KHSO4
  12. temperaturedropwise maintaining the temperature below 10° C
  13. additionA total of 50 ml of the saturated solution was added
  14. customSolids formed in the solution
  15. customwere removed by vacuum filtratration
  16. washThe filter cake was washed with tetrahydrofuran (40 mL) and water (40 mL)
  17. additionEthyl acetate (100 mL) was added
  18. customthe layers separated
  19. washThe organic layer was washed with saturated ammonium chloride (100 mL)
  20. dry with materialdried over sodium sulfate, and solvent
  21. customremoved at reduced pressure
  22. additionwater added
  23. customeventually a precipitate formed
  24. filtrationThe solids were collected by vacuum filtration and air
  25. customdried for about 2 hours

Sources & evidence

ORD record
ord-1047f436c0ba46f2bcf540f338c0cf50
Source dataset
uspto-grants-2012_04
Patent number
US08148409B2

Reaction notes

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