Sodium hydride → (S)-4-Chloro-1-(3-chloro-1-phenyl-propyl)-1H-indole

HRID 250205Notes

Reaction equation

HRID 250205 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].[Cl:13][CH2:14][CH2:15][CH:16](OS(C)(=O)=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C@H:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:15][CH2:14][Cl:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 913454-ChloroindoleHCID 57985877Methanesulfonic acid 3-chloro-1-phenyl-propyl ester

Product 1

HCID 58088413(S)-4-Chloro-1-(3-chloro-1-phenyl-propyl)-1H-indole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-chloroindole (0.222 g) in dry DMF (7.5 ml) was added sodium hydride (0.064 g) at room temperature. The mixture was stirred at the same temperature for 30 minutes and then the crude methanesulfonic acid 3-chloro-1-phenyl-propyl ester from the previous step was dissolved in DMF (5 ml) and added at 0° C. to the reaction mixture and stirred for 2 hours. The reaction mixture was partitioned between ethyl acetate and water, the organic layer was washed twice with water and once with brine, then dried over magnesium sulfate, filtered and evaporated to dryness to afford an oil. Purification of the crude product was done by column chromatography on silica gel, eluting the desired product with ethyl acetate-hexane (1:9). The (S) 4-chloro-1-(3-chloro-1-phenyl-propyl)-1H-indole thus produced weighed 0.251 g, sufficiently pure for use in the following step.

Workup

  1. additionadded at 0° C. to the reaction mixture
  2. stirringstirred for 2 hours
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. washthe organic layer was washed twice with water and once with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customto afford an oil
  9. customPurification of the crude product
  10. washeluting the desired product with ethyl acetate-hexane (1:9)

Sources & evidence

ORD record
ord-00b43d95f8f2418a9335e891c82d3fe3
Source dataset
uspto-grants-2011_01
Patent number
US07863305B2

Reaction notes

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