Tetrahydrofuran → 1-(2,5-Difluoro-4-methoxyphenyl)-4-methoxymethylenepiperidine

HRID 269916

Reaction equation

HRID 269916 reaction equation
[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1.[F:29][C:30]1[CH:35]=[C:34]([O:36][CH3:37])[C:33]([F:38])=[CH:32][C:31]=1[N:39]1[CH2:44][CH2:43][C:42](=O)[CH2:41][CH2:40]1>O>[F:29][C:30]1[CH:35]=[C:34]([O:36][CH3:37])[C:33]([F:38])=[CH:32][C:31]=1[N:39]1[CH2:44][CH2:43][C:42](=[CH:2][O:3][CH3:4])[CH2:41][CH2:40]1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 231114661-(2,5-Difluoro-4-methoxyphenyl)piperidin-4-one

Product 1

HCID 231114001-(2,5-Difluoro-4-methoxyphenyl)-4-methoxymethylenepiperidineYield 34.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A reaction vessel was charged with methoxymethyltriphenyl-phosphonium chloride (1.114 g), the atomosphere indide the vessel was substituted with nitrogen, and anhydrous tetrahydrofuran (2 mL) was added, followed by further dropwise addition of 1.57 M n-butyl lithium-in-hexane solution (2 mL) at room temperature and thereafter 10 minutes' stirring at room temperature. To the reaction mixture a mixture of 1-(2,5-difluoro-4-methoxyphenyl)piperidin-4-one (676 mg) and anhydrous tetrahydrofuran (0.5 mL) was added dropwise, followed by 30 minutes' stirring at room temperature. To the reaction mixture water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline solution and dried over anhydrous sodium sulfate. Distilling the solvent off, the crude product as obtained was purified on silica gel column chromatography (eluent, hexane: ethyl acetate=10:1) to provide 1-(2,5-difluoro-4-methoxyphenyl)-4-methoxymethylenepiperidine (257 mg).

Workup

  1. additionwas added
  2. additionwas added dropwise
  3. waitfollowed by 30 minutes
  4. stirring' stirring at room temperature
  5. extractionfollowed by extraction with ethyl acetate
  6. washThe organic layer was washed with saturated saline solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationDistilling the solvent off, the crude product
  9. customas obtained
  10. customwas purified on silica gel column chromatography (eluent, hexane: ethyl acetate=10:1)

Sources & evidence

ORD record
ord-0354f4e12ffe4f7cad2355f89c6f816a
Source dataset
uspto-grants-2008_11
Patent number
US07449466B2

Linked notes

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