Methyl iodide → HCID 178482467, compound

HRID 1620486Notes

Reaction equation

HRID 1620486 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH:12]=O)[CH2:8][CH2:7]1.[CH3:24]C(C)([O-])C.[K+].CI.[Cl-].[NH4+].[CH3:34][NH:35][C:36]1[CH2:40][S:39][C:38](=[O:41])[N:37]=1>O1CCCC1.C(O)C.C(OCC)(=O)C>[F:1][C:2]([F:23])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][C:9](/[CH:24]=[C:40]2/[C:36]([NH:35][CH3:34])=[N:37][C:38](=[O:41])[S:39]/2)([CH3:12])[CH2:8][CH2:7]1

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 25517Ammonium Chloride2×HCID 23665647Potassium tert-butoxide2×HCID 866786631-[2,4-Bis(trifluoromethyl)benzyl]piperidine-4-carbaldehydeHCID 178482466HCID 178482466, compound

Product 1

HCID 178482467HCID 178482467, compoundYield 16.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 1-[2,4-bis(trifluoromethyl)benzyl]piperidine-4-carbaldehyde (372 mg) in tetrahydrofuran (5 mL) were added potassium tert-butoxide (123 mg) and methyl iodide (0.069 mL) under ice-cooling. The reaction mixture was stirred at room temperature for 1 hr under a nitrogen atmosphere. To the reaction mixture were added saturated aqueous ammonium chloride solution/ethyl acetate, and the organic layer was separated, washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give an oil. The obtained oil and 4-(methylamino)-1,3-thiazol-2(5H)-one (143 mg) were suspended in ethanol (5 mL), and potassium tert-butoxide (123 mg) was added. The reaction mixture was stirred at 80° C. for 3 hr. To the reaction mixture were added saturated aqueous ammonium chloride solution/ethyl acetate at room temperature, and the organic layer was separated, washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and recrystallized from ethyl acetate/heptane to give the title compound (83 mg).

Workup

  1. temperaturecooling
  2. customthe organic layer was separated
  3. washwashed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  7. customto give an oil
  8. stirringThe reaction mixture was stirred at 80° C. for 3 hr
  9. customthe organic layer was separated
  10. washwashed with water and saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  14. customrecrystallized from ethyl acetate/heptane

Sources & evidence

ORD record
ord-7f35b5c9b0c54b2d8376297dac5edaba
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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