Cyclopentadiene → (1S,2R)-2-[(Benzyloxy)methyl]cyclopent-3-en-1-ol

HRID 1742625Notes

Reaction equation

HRID 1742625 reaction equation
[CH:1]1[CH2:5][CH:4]=[CH:3][CH:2]=1.[Na].Cl[CH2:8][O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[B]([C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1)[C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1.[O:38]1CCCC1>>[C:11]1([CH2:10][O:9][CH2:8][C@H:2]2[CH:1]=[CH:5][CH2:4][C@@H:3]2[OH:38])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 5

HCID 7612CyclopentadieneHCID 8028Tetrahydrofuran2×HCID 137983Benzyl chloromethyl etherHCID 5360545SodiumHCID 10989779Bis[(1R,2S,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl]boranyl

Product 1

HCID 10987367(1S,2R)-2-[(Benzyloxy)methyl]cyclopent-3-en-1-ol

Procedure

Cyclopentadiene (39 g., 0.59 mol.) at -20° was added over 35 minutes to a stirred mixture of 31.0 g. of 40% sodium sand in mineral oil (0.54 g. atm.) in 264 ml. of dry tetrahydrofuran at -15°. The mixture was stirred at -10° for 1.5 hours, warmed to 0°, and cannulated to an addition funnel at 0°. The mixture was then added over 30 minutes to a stirred solution of benzyl chloromethyl ether (100 g., 0.64 mol.) in 200 ml. of tetrahydrofuran at -50° to -55°. The mixture was stirred at -55° to -40° for 1 hour and then cooled to -65°. To this was added, by cannula over 5 minutes, the crystalline slurry of (-)-diisopinocampheylborane from step A, which had been cooled to -60°. The reaction was stirred at -60° for 1 hour, warmed to -10° and stored at -20° overnight. The reaction mixture was stirred for 1 hour at 5° and concentrated in vacuo to one half its original volume. Ether (600 ml.) was added, the stirred mixture was cooled to 0°, and 188 ml. of 3N sodium hydroxide was added dropwise keeping the temperature below 5°. Cold 30% hydrogen peroxide (188 ml.) was added dropwise over 1 hour keeping the temperature below 12°, and then the mixture was stirred for 1 hour longer while maintaining the temperature below 12°. The layers were separated, and the aqueous layer was washed with ether. The ether extracts were combined, dried(sodium sulfate), and concentrated in vacuo to a residue (337 g.). Chromatography of this residue on a column of Merck silica gel [2300 g., packed in petroleum ether-ether (2:1)] using petroleum ether-ether (2:1) and then (1:1)]gave fraction A (17.56 g. of impure desired product), fraction B (11.03 g. of pure desired product), and fraction C (3.52 g. of impure desired product). Similar chromatography of fraction A on 800 g. of silica gel, and fraction C on 140 g. of silica gel, gave 8.08 g. and 2.33 g., respectively, of additional pure desired product for a total yield of 21.44 g. of title compound.

Workup

  1. customat -15°
  2. temperaturewarmed to 0°
  3. customcannulated to an addition funnel at 0°
  4. customat -50° to -55°
  5. stirringThe mixture was stirred at -55° to -40° for 1 hour
  6. temperaturecooled to -65°
  7. additionTo this was added, by cannula over 5 minutes
  8. stirringThe reaction was stirred at -60° for 1 hour
  9. temperaturewarmed to -10°
  10. waitstored at -20° overnight
  11. stirringThe reaction mixture was stirred for 1 hour at 5°
  12. concentrationconcentrated in vacuo to one half its original volume
  13. additionEther (600 ml.) was added
  14. temperaturethe stirred mixture was cooled to 0°
  15. additionof 3N sodium hydroxide was added dropwise
  16. customthe temperature below 5°
  17. additionCold 30% hydrogen peroxide (188 ml.) was added dropwise over 1 hour
  18. customthe temperature below 12°
  19. stirringthe mixture was stirred for 1 hour longer
  20. temperaturewhile maintaining the temperature below 12°
  21. customThe layers were separated
  22. washthe aqueous layer was washed with ether
  23. concentrationdried(sodium sulfate), and concentrated in vacuo to a residue (337 g.)
  24. customof silica gel, gave 8.08 g

Sources & evidence

ORD record
ord-99a5746b881049ef9f2f5f1a640abcae
Source dataset
uspto-grants-1994_08
Patent number
US05340816

Reaction notes

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