Methyl iodide → HCID 66650277, compound

HRID 418553Notes

Reaction equation

HRID 418553 reaction equation
[H-].[Na+].C(OC([N:10]1[CH2:15][CH2:14][CH:13]([N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[NH:22][CH:21]=[CH:20]3)[CH2:12][CH2:11]1)=O)(C)(C)C.CI.[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38]>CN(C=O)C.C(Cl)Cl>[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38].[CH2:26]([N:16]([C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH3:36])[CH:21]=[CH:20]2)[CH:13]1[CH2:14][CH2:15][NH:10][CH2:11][CH2:12]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 66650198HCID 66650198, compound

Product 1

HCID 66650277HCID 66650277, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

NaH (60% in mineral oil, 30 mg, 0.74 mmol) was added to a solution of 4-[benzyl-(1H-indol-5-yl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (150 mg, 0.37 mmol) in DMF (1.0 mL). The reaction mixture was stirred for 1 hour and then methyliodide (0.06 mL, 0.93 mmol) was added. The resulting mixture was stirred for 2 hours and it was then quenched by addition of a saturated aqueous solution of NH4Cl. The organic layer was separated and the aqueous layer was extracted twice with EtOAc (20 mL); the combined organic extracts were washed with brine (50 mL), dried over MgSO4, filtered and evaporated under reduced pressure to give a yellow foam. This residue was dissolved in DCM (5 mL) and trifluoroacetic acid (0.29 mL, 3.7 mmol) was added. The resulting mixture was stirred at room temperature for 16 hours; it was then evaporated under reduced pressure and the residue was purified by flash chromatography (0% to 20% of MeOH in DCM) to give 115 mg (97% yield) of benzyl-(1-methyl-1H-indol-5-yl)-piperidin-4-yl-amine trifluoroacetate, MS=320 [M+H]+.

Workup

  1. stirringThe resulting mixture was stirred for 2 hours
  2. customit was then quenched by addition of a saturated aqueous solution of NH4Cl
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted twice with EtOAc (20 mL)
  5. washthe combined organic extracts were washed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give a yellow foam
  10. stirringThe resulting mixture was stirred at room temperature for 16 hours
  11. customit was then evaporated under reduced pressure
  12. customthe residue was purified by flash chromatography (0% to 20% of MeOH in DCM)

Sources & evidence

ORD record
ord-151bf6708c7a4d09ad22650f3c729329
Source dataset
uspto-grants-2012_01
Patent number
US08093285B2

Reaction notes

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