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

HRID 1964084Notes

Reaction equation

HRID 1964084 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]+; 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-5f83adbfc1224d81b1d61f07042b80fb
Source dataset
uspto-grants-2013_04
Patent number
US08415484B2

Reaction notes

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