Methyl iodide → tert-butyl (3S)-4-[2-methoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazine-1-carboxylate

HRID 2178772Notes

Reaction equation

HRID 2178772 reaction equation
[OH:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:8]=2)[CH:3]1[N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C@@H:16]1[CH3:28].[H-].[Na+].[CH3:31]I>C1COCC1>[CH3:31][O:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([F:14])([F:12])[F:13])[CH:8]=2)[CH:3]1[N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C@@H:16]1[CH3:28]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59212650tert-butyl (3S)-4-[2-hydroxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazine-1-carboxylate

Product 1

HCID 59212634tert-butyl (3S)-4-[2-methoxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl (3S)-4-[2-hydroxy-5-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]-3-methylpiperazine-1-carboxylate (isomer 1 from step C in Example 9) (50 mg, 0.1 mmol) in THF (2 mL) at 0° C. was added NaH (8 mg, 60% in oil, 0.2 mmol). After being stirred for 10 min, MeI (28 mg, 0.2 mmol) was added. The mixture was stirred at ambient temperature for 1 h and quenched with aqueous NH4Cl. The resulting solution was extracted with EtOAc twice. The extracts were washed with brine, dried (MgSO4), filtered and concentrated to give the crude product. LC/MS calculated for C21H29F3N2O3: (M+H)+415. found 415.2.

Workup

  1. stirringThe mixture was stirred at ambient temperature for 1 h
  2. customquenched with aqueous NH4Cl
  3. extractionThe resulting solution was extracted with EtOAc twice
  4. washThe extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-a0e9a2636bfb4ce0b577c520d24ef0c7
Source dataset
uspto-grants-2015_06
Patent number
US09067921B2

Reaction notes

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