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-cyclopropyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

HRID 1964100Notes

Reaction equation

HRID 1964100 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+])[CH2:42][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: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]([CH:40]5[CH2:42][CH2:41]5)[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

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 178419765HCID 178419765, compound

Product 1

HCID 86654869tert-Butyl 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-cyclopropyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateYield 21.3%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-9-iodo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (50.0 mg, 0.078 mmol) in THF (1 mL) in a 2.0 mL heavy-walled sealed microwave tube under N2 was added cyclopropylzinc(II) bromide (0.5 M solution in THF, 0.219 mL, 0.109 mmol) and bis(tri-t-butylphosphine)palladium(0) (3.60 mg, 7.04 μmol). The reaction mixture was heated to 70° C. for 2 h, quenched with saturated NaHCO3 and filtered by vacuum filtration through Celite®. The Celite® was washed with EtOAc (2×5 mL). The filtrate was extracted with EtOAc (3×5 mL). The organic layers were combined and washed with saturated NaCl (10 mL), dried over MgSO4, filtered by vacuum filtration. The filtrate was concentrated under reduced pressure. The residue was purified by preparative TLC to give the title compound as a amber oil (9.2 mg). LCMS m/z=554.6 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-7631bb060162439ba041801490c2fcbc
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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