Acetic Acid → HCID 67073393, compound

HRID 493989Notes

Reaction equation

HRID 493989 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][C@H:16]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]3C=CC=CC=3)[CH2:17]1)=[CH:10][CH:9]=2)=[O:5])[CH3:2].[C:28](O)(=O)C.IC(C)C>C(O)C.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][C@H:16]1[CH2:20][CH2:19][N:18]([CH:21]([CH3:22])[CH3:28])[CH2:17]1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 6362Isopropyl iodideHCID 67073446HCID 67073446, compound

Product 1

HCID 67073393HCID 67073393, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a mixture of 5-((S)-1-benzyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl ester (18.0 g, 1.0 eq.) and acetic acid (28 mL, 10 eq.) in ethanol (500 mL) was added palladium on activated charcoal (10% in mass, 2.0 g, 0.04 eq.) and the reaction vessel was flushed with hydrogen (1 Atm). The reaction mixture was stirred 18 h at room temperature and then filtered off and concentrated in vacuo. The residue (28.4 g) was dissolved in dimethylformamide (500 mL) and potassium carbonate was added. The mixture was stirred 15 min at room temperature. Then 2-iodopropane (42 g, 5.0 eq.) was added and the mixture was stirred 4 h at 50° C. The reaction mixture was filtered off and the filtrate was evaporated in vacuo. The residue was dissolved in acetone, filtered and the filtrate was evaporated in vacuo then purified on silica eluting with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 9.3 g (59%) of the desired product as light brown solid. MS (m/e): 317.4 (MH+, 100%).

Workup

  1. customthe reaction vessel was flushed with hydrogen (1 Atm)
  2. filtrationfiltered off
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue (28.4 g) was dissolved in dimethylformamide (500 mL)
  5. additionpotassium carbonate was added
  6. stirringThe mixture was stirred 15 min at room temperature
  7. stirringthe mixture was stirred 4 h at 50° C
  8. filtrationThe reaction mixture was filtered off
  9. customthe filtrate was evaporated in vacuo
  10. dissolutionThe residue was dissolved in acetone
  11. filtrationfiltered
  12. customthe filtrate was evaporated in vacuo
  13. customthen purified on silica eluting with dichloromethane/methanol/ammoniac
  14. customOne fraction was isolated
  15. customdried in vacuo

Sources & evidence

ORD record
ord-80392c0832804e07a176d4189e6b9f5e
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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