Diethyl Ether → HCID 15512819, compound

HRID 1633574Notes

Reaction equation

HRID 1633574 reaction equation
C([Li])CCC.BrC1C=[CH:11][C:10]([F:13])=[CH:9][C:8]=1OC.[CH2:16]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH2:30]([O:32][CH2:33][CH3:34])C>>[CH2:16]([N:23]1[CH2:28][CH2:27][C:26]([C:8]2[CH:9]=[C:10]([F:13])[CH:11]=[CH:34][C:33]=2[O:32][CH3:30])([OH:29])[CH2:25][CH2:24]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

5

Reactant 4

HCID 3283Diethyl Ether3×HCID 192201-Benzyl-4-piperidoneHCID 70180432-Bromo-5-fluoroanisoleHCID 178418339Butyllithium

Product 1

HCID 15512819HCID 15512819, compoundYield 68%

Conditions

Temperature
-50 °C

Procedure

To a solution of 9.8 mL (24 mmole) butyllithium (2.5 M solution in hexane) in diethylether (20 mL) under N. at −78° C. was slowly added 2-bromo-5-fluoroanisole (5.0 g, 24 mmole) in diethylether (5 mL). The mixture was allowed to warm up to −50° C. At this point, 1-benzyl-4-piperidone (4.62 g, 24.4 mmole) in diethylether (3 mL) was added. The resulting mixture was allowed to stirred at −50° C. for 30 minutes, and then warmed to room temperature. The reaction was quenched by dropwise addition of saturated NH4Cl solution. The mixture was then transferred to a separatory funnel, the layers were separated and the aqueous was extracted three times with EtOAc. The combined organic phase was dried over Na2SO4, filtered and concentrated. Flash chromatography (elution with 7:3 EtOAc-hexanes) afforded 5.27 g (68%) of 1-benzyl-4-(5-fluoro-2-methoxy-phenyl)-4-hydroxypiperidine as a yellow oil.

Workup

  1. customat −78° C.
  2. temperaturewarmed to room temperature
  3. customThe reaction was quenched by dropwise addition of saturated NH4Cl solution
  4. customThe mixture was then transferred to a separatory funnel
  5. customthe layers were separated
  6. extractionthe aqueous was extracted three times with EtOAc
  7. dry with materialThe combined organic phase was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washFlash chromatography (elution with 7:3 EtOAc-hexanes)

Sources & evidence

ORD record
ord-a84e3a854326423da799d986ddab85aa
Source dataset
uspto-grants-2003_01
Patent number
US06503928B2

Reaction notes

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