tert-Butyl 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate → tert-Butyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-cyclobutyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

HRID 515685Notes

Reaction equation

HRID 515685 reaction equation
[CH:1]1([C:6]2[CH:34]=[CH:33][C:9]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][C:18]4[N:17]5[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:16]5=[C:15](I)[C:14]=4[CH:13]=3)=[CH:8][C:7]=2[C:35]([F:38])([F:37])[F:36])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Br-].[CH:40]1([Zn+])[CH2:43][CH2:42][CH2:41]1>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:40]1([C:15]2[C:14]3[CH:13]=[C:12]([O:11][CH2:10][C:9]4[CH:33]=[CH:34][C:6]([CH:1]5[CH2:5][CH2:4][CH2:3][CH2:2]5)=[C:7]([C:35]([F:38])([F:37])[F:36])[CH:8]=4)[CH:20]=[CH:19][C:18]=3[N:17]3[CH2:21][CH2:22][CH:23]([CH2:24][C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[C:16]=23)[CH2:43][CH2:42][CH2:41]1

Participants

5

Reactant 2

HCID 67249572tert-Butyl 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateHCID 178419766HCID 178419766, compound

Product 1

HCID 86654870tert-Butyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-cyclobutyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateYield 39.1%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

tert-Butyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (50 mg, 0.078 mmol) was dissolved in THF (1.0 mL) in a heavy walled sealed microwave tube (0.5-2.0 mL) under N2. Cyclobutylzinc(II) bromide (0.156 mL, 0.078 mmol) and bis(tri-t-butylphosphine)palladium(0) (3.60 mg, 7.04 μmol) were added. The reaction mixture was heated to 70° C. for 2 h, quenched with saturated NaHCO3 and filtered through Celite®. The filtrate was then extracted with EtOAc (3×5 mL). The organic layers were combined and washed with saturated NaCl (10 mL), dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC to provide the title compound as an amber oil (17.3 mg). LCMS m/z=568.8 [M+H]+.

Workup

  1. customquenched with saturated NaHCO3
  2. filtrationfiltered through Celite®
  3. extractionThe filtrate was then extracted with EtOAc (3×5 mL)
  4. washwashed with saturated NaCl (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-ac994fde278d4d76810b9651e8a39dda
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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