Cesium carbonate → 5-Benzyloxy-1-isopropyl-1H-indole-2-carboxylic acid ethyl ester

HRID 494003Notes

Reaction equation

HRID 494003 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][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH:29](CS([O-])(=O)=O)([CH3:31])[CH3:30]>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH:29]([CH3:31])[CH3:30])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 95721Ethyl 5-(phenylmethoxy)-1H-indole-2-carboxylateHCID 22141912Isopropyl-methanesulfonate

Product 1

HCID 670735335-Benzyloxy-1-isopropyl-1H-indole-2-carboxylic acid ethyl esterYield 90.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 5-benzyloxyindole-2-carboxylic acid ethyl ester (30 g, 1.0 eq.) and cesium carbonate (58. g, 1.75 eq.) in acetonitrile (200 mL), was added isopropylmethane sulfonate (24.8 g, 1.75 eq.). The reaction mixture was refluxed for 18 h and then concentrated in vacuo. The residue was partitioned between water and methyl-tert-butylether. The aqueous layer was extracted with methyl-tert-butylether and the combined organic layers were washed with brine, dried over sodium sulfate, filtered and dried in vacuo. then purified on silica eluting with dichloromethane/methanol 98:2 v:v. The crude material was purified by crystallization in ethanol and dried in vacuo to yield 31 g (90%) of the desired product as an off-white oil. MS (m/e): 338.4 (MH+, 100%).

Workup

  1. temperatureThe reaction mixture was refluxed for 18 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between water and methyl-tert-butylether
  4. extractionThe aqueous layer was extracted with methyl-tert-butylether
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customdried in vacuo
  9. customthen purified on silica eluting with dichloromethane/methanol 98:2 v
  10. customThe crude material was purified by crystallization in ethanol
  11. customdried in vacuo

Sources & evidence

ORD record
ord-6ef893ad90dc4d9782d057d0d3e6777c
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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