Methyl iodide → HCID 117839465, compound

HRID 1477581Notes

Reaction equation

HRID 1477581 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:24]I.[Cl-].[NH4+]>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH3:24])[CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 16413902tert-Butyl 4-(4-fluoroanilino)piperidine-1-carboxylate

Product 1

HCID 117839465HCID 117839465, compoundYield 109.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an N,N-dimethylformamide solution (5 ml) of tert-butyl 4-[(4-fluorophenyl)amino]piperidine-1-carboxylate (250 mg, 0.850 mmol) synthesized in Reference Synthesis Example 23, sodium hydride (37 mg, 0.93 mmol, purity 60%) and methyl iodide (58 μL, 0.93 mmol) were added at room temperature and the resultant solution was stirred at room temperature for 15 hours. After completion of the reaction, saturated ammonium chloride aqueous solution was added, and extraction with ethyl acetate was performed from the resultant mixture. The resultant organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a crude product of tert-butyl 4-[(4-fluorophenyl)(methyl)amino]piperidine-1-carboxylate (286 mg). Subsequently, to the obtained tert-butyl 4-[(4-fluorophenyl)(methyl)amino]piperidine-1-carboxylate (130 mg, 0.420 mmol), 4 M hydrogen chloride/1,4-dioxane solution (2 mL) was added and the resultant mixture was stirred at room temperature for 1 day. After completion of the reaction, the resultant solid was collected by filtration and washed with dichloromethane. To the obtained solid, water was added and pH of the resultant solution was adjusted to 9 with 1 M sodium hydroxide aqueous solution, followed by extraction from the resultant mixture with ethyl acetate and chloroform. The obtained organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the title compound (62 mg, yield 72%).

Workup

  1. additionwere added at room temperature
  2. additionwas added
  3. extractionextraction with ethyl acetate
  4. dry with materialThe resultant organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fa7383bd9e7e46f98f18ca1caf92bb94
Source dataset
uspto-grants-2016_08
Patent number
US09403798B2

Reaction notes

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