Ethyl 2-(2-oxocyclopentyl)acetate → Ethyl 2-(7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetate

HRID 2250532Notes

Reaction equation

HRID 2250532 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4](I)[CH:3]=1.O=[C:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:20]([O:19][C:17](=[O:18])[CH2:16][CH:12]1[C:11]2[NH:6][C:5]3[CH:7]=[CH:8][C:2]([F:1])=[CH:3][C:4]=3[C:15]=2[CH2:14][CH2:13]1)[CH3:21]

Participants

5

Reactant 2

HCID 2723663Ethyl 2-(2-oxocyclopentyl)acetateHCID 27782834-Fluoro-2-iodoaniline

Product 1

HCID 11276987Ethyl 2-(7-fluoro-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetateYield 53.1%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 241BenzeneSolvent

Conditions

Temperature
115 °C

Procedure

A solution of 10.00 g of 4-fluoro-2-iodoaniline, 6.57 g of ehtyl 2-(2-oxocyclopentyl)acetate and 121 mg of p-toluenesulfonic acid in 100 ml of benzene was refluxed with a Dean-Stark trap under a N2 atmosphere for 24 h. After this time, the benzene was removed under distillation. Then, 60 ml of DMF was added and the solution was degassed before 19 ml of Hunig's base followed by 405 mg of Pd(OAc)2 were added successively. The solution was heated to 115° C. for 3 h, then cooled to room temperature. To quench the reaction, 300 ml of 1 N HCl and 200 ml of ethyl acetate were added and the mixture was filtered through Celite. The phases were separated and the acidic phase was extracted twice with 200 ml of ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous Na2SO4, filtered through Celite and concentrated. The crude material was further purified by flash chromatography eluting with 100% toluene to provide 5.36 g of the title compound as a yellow solid.

Workup

  1. customAfter this time, the benzene was removed under distillation
  2. additionThen, 60 ml of DMF was added
  3. customthe solution was degassed before 19 ml of Hunig's base
  4. additionwere added successively
  5. temperaturecooled to room temperature
  6. customTo quench
  7. customthe reaction, 300 ml of 1 N HCl and 200 ml of ethyl acetate
  8. additionwere added
  9. filtrationthe mixture was filtered through Celite
  10. customThe phases were separated
  11. extractionthe acidic phase was extracted twice with 200 ml of ethyl acetate
  12. washwashed with brine
  13. dry with materialdried over anhydrous Na2SO4
  14. filtrationfiltered through Celite
  15. concentrationconcentrated
  16. customThe crude material was further purified by flash chromatography
  17. washeluting with 100% toluene

Sources & evidence

ORD record
ord-9280d16ca67840948081d92a066711d5
Source dataset
uspto-grants-2008_01
Patent number
US07317036B2

Reaction notes

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