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

HRID 515668

Reaction equation

HRID 515668 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[CH2:11][CH2:12][CH:13]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6]3=[CH:5][C:4]=2[CH:3]=1.Cl[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[C:26]([C:35]([F:38])([F:37])[F:36])[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH:30]1([C:27]2[CH:28]=[CH:29][C:24]([CH2:23][O:1][C:2]3[CH:10]=[CH:9][C:8]4[N:7]5[CH2:11][CH2:12][CH:13]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:6]5=[CH:5][C:4]=4[CH:3]=3)=[CH:25][C:26]=2[C:35]([F:36])([F:37])[F:38])[CH2:31][CH2:32][CH2:33][CH2:34]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 534026024-(Chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzeneHCID 67249455tert-butyl 2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 67248866tert-Butyl 2-(7-(4-Cyclopentyl-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateYield 62.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl 2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (0.563 g, 1.960 mmol), 4-(chloromethyl)-1-cyclopentyl-2-(trifluoromethyl)benzene (0.515 g, 1.960 mmol) and cesium carbonate (0.703 g, 2.156 mmol) in DMF (4 mL) were heated to 50° C. for 16 h in a 20 mL sealed scintillation vial. The reaction mixture was filtered by vacuum filtration through Celite® and washed with EtOAc (3×10 mL). The filtrate was concentrated under reduced pressure. The residue was taken up in EtOAc (25 mL), washed with water (2×25 mL), saturated NaCl (20 mL), dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to give a yellow sticky oil. A precipitate, formed by addition of hexanes to the oil, was collected by filtration, was washed with hexanes (3×20 mL) and dried (vacuum oven) to provide the title compound as a white solid (0.6273 g). LCMS m/z=514.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (s, 9H), 1.57-1.72 (m, 4H), 1.81-1.87 (m, 2H), 1.95-2.04 (m, 2H), 2.15-2.24 (m, 1H), 2.53-2.67 (m, 2H), 2.71-2.81 (m, 1H), 3.20-3.27 (m, 1H), 3.57 (quintet, J=7.75 Hz, 1H), 3.91-3.99 (m, 1H), 4.06-4.13 (m, 1H), 5.13 (s, 2H), 5.99 (s, 1H), 6.77 (dd, J=8.65, 2.08 Hz, 1H), 7.07 (d, J=2.27 Hz, 1H), 7.19 (d, J=8.72 Hz, 1H), 7.62 (d, J=8.72 Hz, 1H) 7.68-7.70 (m, 2H).

Workup

  1. customsealed scintillation vial
  2. filtrationThe reaction mixture was filtered by vacuum filtration through Celite®
  3. washwashed with EtOAc (3×10 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. washwashed with water (2×25 mL), saturated NaCl (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography
  10. customto give a yellow sticky oil
  11. filtrationwas collected by filtration
  12. washwas washed with hexanes (3×20 mL)
  13. customdried (vacuum oven)

Sources & evidence

ORD record
ord-898b5838fa8d4be29421e5ee8a6678b6
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Linked notes

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