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

HRID 515666Notes

Reaction equation

HRID 515666 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:25]=[CH:26][C:27]([O:32][CH:33]([CH3:35])[CH3:34])=[C:28]([CH:31]=1)[C:29]#[N:30].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:29]([C:28]1[CH:31]=[C:24]([CH:25]=[CH:26][C:27]=1[O:32][CH:33]([CH3:35])[CH3:34])[CH2:23][O: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)#[N:30]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 668477035-(Chloromethyl)-2-(propan-2-yloxy)benzonitrileHCID 67249455tert-butyl 2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

Product 1

HCID 67252091tert-Butyl 2-(7-(3-cyano-4-isopropoxybenzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetateYield 62.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl 2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (461 mg, 1.60 mmol) was dissolved in DMF (3.0 mL) and 5-(chloromethyl)-2-isopropoxybenzonitrile (337 mg, 1.60 mmol) and cesium carbonate (533 mg, 1.60 mmol) were added. The reaction mixture was stirred at room temperature for 2 days and partitioned between ethyl acetate and water. The organics were removed and the aqueous mixture was extracted two times with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The residual oil was dissolved in methanol (10 mL) and cooled to 0° C. The precipitate was collected by filtration and triturated with 10% ethyl acetate/hexanes to provide the title compound (462 mg). LCMS m/z=461.5 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.31 (d, J=6.1 Hz, 6H), 1.44 (s, 9H), 2.15-2.25 (m, 1H), 2.51-2.68 (m, 2H), 2.71-2.81 (m, 1H), 3.53-3.61 (m, 1H), 3.91-3.99 (m, 1H), 4.04-4.13 (m, 1H), 4.78 (septet, J=6.1 Hz, 1H), 5.02 (s, 2H), 5.99 (s, 1H), 6.74 (dd, J=8.7, 2.4 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 7.18 (d, J=8.7 Hz, 1H), 7.27 (d, J=9.0 Hz, 1H), 7.70 (dd, J=8.7, 2.3 Hz, 1H), 7.76 (d, J=2.1 Hz, 1H).

Workup

  1. custompartitioned between ethyl acetate and water
  2. customThe organics were removed
  3. extractionthe aqueous mixture was extracted two times with ethyl acetate
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residual oil was dissolved in methanol (10 mL)
  8. temperaturecooled to 0° C
  9. filtrationThe precipitate was collected by filtration
  10. customtriturated with 10% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-fb6674c9c46c4487b03addb362d18b47
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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