Acetic Acid → (R)-3-(3-benzyloxybenzyl)-4-oxocyclopent-2-enyl acetate

HRID 1803639Notes

Reaction equation

HRID 1803639 reaction equation
[OH:1][CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:10]=2)=[CH:3]1.[C:23](OC=C)(=[O:25])[CH3:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(O)=O.CC(OC(/N=N/C(OC(C)C)=O)=O)C>CC(CC(C)C)=O>[C:23]([O:1][C@@H:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:10]=2)=[CH:3]1)(=[O:25])[CH3:24]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7904Vinyl AcetateHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 711700344-Hydroxy-2-(3-benzyloxybenzyl)cyclopent-2-enone

Product 1

HCID 71170042(R)-3-(3-benzyloxybenzyl)-4-oxocyclopent-2-enyl acetateYield 75%

Reagents, catalysts & solvents 1

HCID 7909Methyl Isobutyl KetoneSolvent

Procedure

4-Hydroxy-2-(3-Benzyloxybenzyl)cyclopent-2-enone (2.1 kg, 7.14 mol) was dissolved in isobutyl methyl ketone (21 L), and vinyl acetate (4.2 kg, 51.16 mol) and Lipase derived from Pseudomonas cepacia (210 g) was added to the solution, and the mixture was stirred at room temperature for 1 day. The reaction mixture was filtered to remove Lipase and the filtrate was evaporated. The resulting residue was dissolved in PhCH3 (20 L), and triphenylphosphine (625 g, 2.38 mol) and AcOH (145 g, 2.41 mol) was added to the solution. Then diisopropylazodicarboxylate (413 g, 2.04 mol) was added to the mixture at 5° C. After the reaction was completed, the reaction mixture was filtered to remove the precipitate and the filtrate was evaporated. The residue was dissolved in EtOAc (5 L) and hexane (5 L) was added. The mixture was stirred at room t temperature overnight. The mixture was filtered to remove the precipitate and the filtrate was evaporated. The residue was purified by chromatography on a silica gel column using hexane-EtOAc as eluent to give the (R)-3-(3-benzyloxybenzyl)-4-oxocyclopent-2-enyl acetate as yellow oil: 1.8 kg (yield: 75%, 97% ee by HPLC using a chiral column)

Workup

  1. additionwas added to the solution
  2. filtrationThe reaction mixture was filtered
  3. customto remove Lipase
  4. customthe filtrate was evaporated
  5. dissolutionThe resulting residue was dissolved in PhCH3 (20 L)
  6. filtrationthe reaction mixture was filtered
  7. customto remove the precipitate
  8. customthe filtrate was evaporated
  9. dissolutionThe residue was dissolved in EtOAc (5 L)
  10. additionhexane (5 L) was added
  11. stirringThe mixture was stirred at room t temperature overnight
  12. filtrationThe mixture was filtered
  13. customto remove the precipitate
  14. customthe filtrate was evaporated
  15. customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-1cc81f4ae47e40b38c84fb689e757f01
Source dataset
uspto-grants-2013_01
Patent number
US08350090B1

Reaction notes

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