HCID 68705549, compound → HCID 68703840, compound

HRID 732313Notes

Reaction equation

HRID 732313 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:14]=[CH:13][C:12]2[O:11][CH:10]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:17][CH:16]=3)[CH:9]3[CH2:25][C:26](=[O:28])[CH2:27][CH:8]3[C:7]=2[CH:6]=1.[CH2:29]([Mg]Cl)[CH3:30]>C1COCC1>[CH2:29]([C:26]1([OH:28])[CH2:25][CH:9]2[CH:10]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:22][O:23][CH3:24])=[CH:19][CH:20]=3)[O:11][C:12]3[CH:13]=[CH:14][C:5]([O:4][CH2:3][O:2][CH3:1])=[CH:6][C:7]=3[CH:8]2[CH2:27]1)[CH3:30]

Participants

4

Reactant 2

HCID 68705549HCID 68705549, compoundHCID 178461633HCID 178461633, compound

Product 1

HCID 68703840HCID 68703840, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

Heat CeCl3-7H2O (97 mg, 0.26 mmol) under vacuum at 70° C. for two hours and then warm slowly to 120° C. and continue heating overnight. Cool to room temperature and add THF (3 mL) followed by cyclopentanone 23 (100 mg, 0.26 mmol) and stir the solution for 45 minutes. Cool the reaction to −10° C., add EtMgCl (3.0 M in THF, 87 ul, 0.26 mmol) and stir the reaction for 30 minutes. Quench the reaction with saturated aqueous NH4Cl and extract with EtOAc (2×). Combine the organic extracts, wash with brine, dry (Na2SO4), filter and concentrate. Purify by flash chromatography (10 g silica gel, 40 mL/min, dry loading on 700 mg of silica gel, 0-30% EtOAc/hexanes for 20 minutes and 30% EtOAc/hexanes for 13 minutes) to afford Alcohol 31 (86 mg, 0.207 mmol, 81%). 1H NMR (δ, 400 MHz, CDCl3) 7.36 (d, 2H, J=8.8 Hz), 7.05 (d, 2H, J=8.8 Hz), 6.90-6.87 (m, 2H), 6.83 (dd, 1H, J=8.8, 2.6 Hz), 5.19 (s, 2H), 5.14 (d, 1H, J=6.8 Hz), 5.10 (d, 1H, J=6.8 Hz), 5.05 (d, 1H, J=2.2 Hz), 3.54 (dd, 1H, J=7.6, 7.6 Hz), 3.51 (s, 3H), 3.49 (s, 3H), 2.70 (ddd, 1H, J=2.2, 7.6, 9.6 Hz), 2.22 (dd, 1H, J=13.6, 7.9 Hz), 2.03 (d, 1H, J=13.6 Hz), 1.84 (dd, 1H, J=14.1, 10.1 Hz), 1.67 (dd, 1H, J=14.1, 9.2 Hz), 1.52 (m, 2H), 0.89 (t, 3H, J=7.3 Hz).

Workup

  1. temperaturecontinue heating overnight
  2. temperatureCool to room temperature
  3. temperatureCool
  4. customthe reaction to −10° C.
  5. stirringstir
  6. customthe reaction for 30 minutes
  7. customQuench
  8. customthe reaction with saturated aqueous NH4Cl
  9. extractionextract with EtOAc (2×)
  10. washCombine the organic extracts, wash with brine
  11. dry with materialdry (Na2SO4)
  12. filtrationfilter
  13. concentrationconcentrate
  14. customPurify by flash chromatography (10 g silica gel, 40 mL/min, dry loading on 700 mg of silica gel, 0-30% EtOAc/hexanes for 20 minutes and 30% EtOAc/hexanes for 13 minutes)

Sources & evidence

ORD record
ord-b83ffd61ba1743e2abe7060fdf81a5ee
Source dataset
uspto-grants-2009_09
Patent number
US07585985B2

Reaction notes

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