Veratrole → (2,3-Dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol

HRID 612423Notes

Reaction equation

HRID 612423 reaction equation
[C:1]1([O:9][CH3:10])[C:2](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O:3][CH3:4].[Li]CCCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][CH:28]([CH:31]=[O:32])[CH2:27][CH2:26]2)=[CH:19][CH:18]=1>C1COCC1.CCCCCC>[CH3:4][O:3][C:2]1[C:1]([O:9][CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH:31]([CH:28]1[CH2:29][CH2:30][N:25]([CH2:24][CH2:23][C:20]2[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=2)[CH2:26][CH2:27]1)[OH:32]

Participants

6

Reactant 3

HCID 7043VeratroleHCID 153921191-[2-(4-Fluorophenyl)ethyl]-4-piperidinecarboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 60858(2,3-Dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of veratrole (0.93 g, 6.7 mmol) in THF (20 mL) under argon at 0° C. was added n-BuLi (2.7 mL of a 2.5 M solution in hexane, 6.75 mmol). After stirring 2.5 h, the solution was cooled to -78° C. and treated with 1-[2-(4-fluorophenyl)ethyl]-4-piperidinecarboxaldehyde (1.30 g, 5.5 mmol) in THF (25 mL) via an addition funnel. The cooling bath was removed and the solution was allowed to stir for 2 hours. Water was added, the layers separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and chromatographed on silica gel, eluting with acetone. The appropriate fractions were combined and evaporated to afford a white solid. The solid was recrystallized from hexane to afford racemic α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol as shiny white needles, m.p. 126-127° C. Anal. Calcd for C22H28FNO3 : C, 70.75; H, 7.56; N, 3.75. Found: C, 70.87; H, 7.65; N, 3.68.

Workup

  1. customThe cooling bath was removed
  2. stirringto stir for 2 hours
  3. additionWater was added
  4. customthe layers separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customchromatographed on silica gel
  10. washeluting with acetone
  11. customevaporated
  12. customto afford a white solid
  13. customThe solid was recrystallized from hexane

Sources & evidence

ORD record
ord-bd8899d082024ae59b4323db3c62e811
Source dataset
uspto-grants-1999_12
Patent number
US06004980

Reaction notes

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