Cesium carbonate → 5-(5-Benzenesulfonyloxy-2-chlorobenzyloxy)-1-[(2-thiophen-3-yl)ethyl]-1h-indole-2-carboxylic acid ethyl ester

HRID 434019Notes

Reaction equation

HRID 434019 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:16][CH2:17][C:18]2[CH:22]=[CH:21][S:20][CH:19]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([OH:15])=[CH:10][CH:9]=2)=[O:5])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:30][C:31]1[CH:32]=[C:33]([O:38][S:39]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)(=[O:41])=[O:40])[CH:34]=[CH:35][C:36]=1[Cl:37]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:16][CH2:17][C:18]2[CH:22]=[CH:21][S:20][CH:19]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:30][C:31]1[CH:32]=[C:33]([O:38][S:39]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)(=[O:40])=[O:41])[CH:34]=[CH:35][C:36]=1[Cl:37])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 120944625-Hydroxy-1-[(2-thiophen-3-yl)ethyl]-1h-indole-2-carboxylic acid ethyl esterHCID 12094463Benzenesulfonic acid 3-bromomethyl-4-chlorophenyl ester

Product 1

HCID 591195095-(5-Benzenesulfonyloxy-2-chlorobenzyloxy)-1-[(2-thiophen-3-yl)ethyl]-1h-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-hydroxy-1-[(2-thiophen-3-yl)ethyl]-1H-indole-2-carboxylic acid ethyl ester (0.42 g, 1.33 mmol) in dry DMF (10 mL) was added Cs2CO3 (0.65 g, 1.99 mmol). After stirring at 60° C. for 30 min, benzenesulfonic acid 3-bromomethyl-4-chlorophenyl ester (0.48 g, 1.33 mmol), from Example 1(b) above, was added. The reaction was kept stirring at 60° C. for 18 h. The reaction mixture was cooled and partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacua. Purification by flash column chromatography (silica gel, EtOAc/hexanes) afforded the partially purified product which was used directly in the next step without further purification (see Examples 1(h) and 2(c)).

Workup

  1. stirringThe reaction was kept stirring at 60° C. for 18 h
  2. temperatureThe reaction mixture was cooled
  3. custompartitioned between EtOAc and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacua
  7. customPurification by flash column chromatography (silica gel, EtOAc/hexanes)
  8. customafforded the partially purified product which
  9. customwas used directly in the next step without further purification (see Examples 1(h) and 2(c))

Sources & evidence

ORD record
ord-45de1a0aad764a9e9faed0bb238ad83a
Source dataset
uspto-grants-2003_12
Patent number
US06670388B1

Reaction notes

Loading…