Sodium Hydroxide → 1-Benzyl-4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydropyridine

HRID 1978831Notes

Reaction equation

HRID 1978831 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[O:22][CH3:23])(O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)(=O)C.S(=O)(=O)(O)O.CCOC(C)=O.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[O:22][CH3:23])=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 14798Sodium HydroxideHCID 15512819HCID 15512819, compound2×

Product 1

HCID 155128201-Benzyl-4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydropyridineYield 65.2%

Reagents, catalysts & solvents 4

HCID 1118Sulfuric AcidCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-benzyl-4-(5-fluoro-2-methoxy-phenyl)-4-hydroxypiperidine (1.01 g, 3.20 mmole) (Intermediate 1) in acetic acid (40 mL) at room temperature was added 2 drops of concentrated sulfuric acid. The resulting solution was heated to reflux, and the mixture stirred for 2 days. The mixture was cooled to room temperature and diluted with EtOAc (100 mL) and water (100 mL). The solution was basified with 50% NaOH solution until pH=10. The layers were separated and the organics washed with brine. The combined aqueous layers were extracted three times with EtOAc (50 mL). The combined organic layers were dried over Na2SO4 and concentrated. Flash chromatography (elution with 1:1 EtOAc-hexane) to give 0.62 g (65%) of 1-benzyl-4-(5-fluoro-2-methoxy-phenyl)-1,2,5,6-tetrahydropyridine as a yellow oil.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux
  3. customThe layers were separated
  4. washthe organics washed with brine
  5. extractionThe combined aqueous layers were extracted three times with EtOAc (50 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. washFlash chromatography (elution with 1:1 EtOAc-hexane)

Sources & evidence

ORD record
ord-1efab397ffbc4ab3b627dfd92d1e9432
Source dataset
uspto-grants-2001_05
Patent number
US06239126B1

Reaction notes

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