1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl ester → alpha-[1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinyl]-alpha-(thiophene-2-yl)-2-thiophenemethanol

HRID 1450441Notes

Reaction equation

HRID 1450441 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]([O:19]C)=O)[CH2:13][CH2:12]2)=[CH:5][CH:4]=1.[Li][C:22]1[S:23][CH:24]=[CH:25][CH:26]=1>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH:14]([C:17]([C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)([C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)[OH:19])[CH2:15][CH2:16]2)=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 108695871-[2-(4-Methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl esterHCID 178418439HCID 178418439, compound2×

Product 1

HCID 18930379alpha-[1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinyl]-alpha-(thiophene-2-yl)-2-thiophenemethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Dissolve 1-[2-(4-methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl ester (4.0 g, 14.42 mmol) in anhydrous tetrahydrofuran (100 mL), place under an argon atmosphere and cool to -78° C. Add, by dropwise addition, 2-lithiothiophene (14.42 mL of a 1M solution in tetrahydrofuran, 14.42 mmol) and stir at -78° C. for 3 hours. Add additional 2-lithiothiophene (14.42 mL of a 1M solution in tetrahydrofuran, 14.42 mmol) and stir at -78°C. for 2 hours. Remove the ice bath and allow to warm to room temperature. Quench with saturated ammonium chloride (100 mL), separate the organic phase and extract the aqueous phase with ethyl acetate. Combine the organic phases, dry (MgSO4) and evaporate the solvent in vacuo. Purify by chromatography (ethyl acetate) and recrystallize (ethyl acetate) to give the title compound as fluffy white crystals; mp 153°-155° C.

Workup

  1. stirringstir at -78°C. for 2 hours
  2. customRemove the ice bath
  3. temperatureto warm to room temperature
  4. customQuench with saturated ammonium chloride (100 mL)
  5. customseparate the organic phase
  6. extractionextract the aqueous phase with ethyl acetate
  7. dry with materialdry (MgSO4)
  8. customevaporate the solvent in vacuo
  9. customPurify by chromatography (ethyl acetate)
  10. customrecrystallize (ethyl acetate)

Sources & evidence

ORD record
ord-155c29c7d0904112a5f2f9f06e309855
Source dataset
uspto-grants-1997_02
Patent number
US05602147

Reaction notes

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