Cesium carbonate → ethyl((1S)-5-{3-[(1-methyl-1H-indol-5-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603393Notes

Reaction equation

HRID 603393 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([OH:11])=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.Br[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[C@H:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]2.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][CH2:13][CH2:14][CH2:15][O:16][C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[C@H:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]4)=[CH:8][CH:9]=2)[CH:4]=[CH:3]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 108445251-Methyl-1H-indol-5-olHCID 16110497ethyl[(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate

Product 1

HCID 59300453ethyl((1S)-5-{3-[(1-methyl-1H-indol-5-yl)oxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetateYield 46.5%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 1-methyl-1H-indol-5-ol (44.0 mg, 0.30 mmol) (Example 47) and ethyl [(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 45, 100 mg, 0.29 mmol) in DMF (4.0 mL) were added Cs2CO3 (114.6 mg, 0.35 mmol) and water (3 drops). The reaction mixture was stirred at 40° C. for 16 h, then cooled to rt, and concentrated under reduced pressure. Water was added and the aqueous layer was extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/Hexane (v/v)=1:13) yielded 55 mg (46%) of the title compound as a clear oil. 1H NMR (400 MHz, CDCl3): δ 1.28 (t, 3H), 1.76 (m, 1H), 2.26 (m, 2H), 2.39 (m, 2H), 2.71 (dd, 1H), 2.88 (m, 2H), 3.50 (m, 1H), 3.78 (s, 3H), 4.18 (m, 6H), 6.38 (d, 1H), 6.72 (dd, 1H), 6.80 (s, 1H), 6.89 (d, 1H), 7.02 (s, 1H), 7.06 (d, 1H), 7.10 (s, 1H), 7.20 (d, 1H).

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated under reduced pressure
  3. additionWater was added
  4. extractionthe aqueous layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel flash chromatography (EtOAc/Hexane (v/v)=1:13)

Sources & evidence

ORD record
ord-443451090e454354a32966d195f99fd9
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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