Acetone → 2-Methyl-7-benzyloxy indole

HRID 480578Notes

Reaction equation

HRID 480578 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[OH:11].CC(C)=O.[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.O>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][C:5]=2[O:11][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 7498Benzyl Bromide2×HCID 10796Cesium carbonate2×HCID 187652222-methyl-1H-indol-7-ol

Product 1

HCID 187653452-Methyl-7-benzyloxy indoleYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To the compound from step A, acetone (15 mL) was added followed by benzyl bromide (670 μL, 5.6 mmol) and Cs2CO3 (1.8 g, 5.6 mmol) and the reaction mixture stirred at RT for 18 h. A second aliquot of BnBr (140 μL) and Cs2CO3 (380 mg) was added and stirring continued for 24 h. The reaction mixture was poured into EtOAc and water, the layers were separated, and the aqueous layer was further extracted with EtOAc (3×50 mL). The combined organic extracts were washed with 1N NaOH and water and dried over MgSO4, filtered, and concentrated in vacuo. Purification by column chromatography (hexanes then 5% EtOAc/hex) afforded 2-methyl-7-benzyloxy indole as an unstable solid (898 mg, 81% yield). 1H NMR impure; 238.17, M+H.

Workup

  1. stirringstirring
  2. waitcontinued for 24 h
  3. customthe layers were separated
  4. extractionthe aqueous layer was further extracted with EtOAc (3×50 mL)
  5. washThe combined organic extracts were washed with 1N NaOH and water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by column chromatography (hexanes

Sources & evidence

ORD record
ord-c54f0a7061fa4f24b3aeccd3efeb7125
Source dataset
uspto-grants-2003_11
Patent number
US06653304B2

Reaction notes

Loading…