Hexane → [1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinyl]methanone

HRID 1165210Notes

Reaction equation

HRID 1165210 reaction equation
FC1C=CC(CN2C3C=CC=CC=3N=C2)=CC=1.CCCCCC.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][N:34]2[CH2:39][CH2:38][CH:37]([C:40](OC)=[O:41])[CH2:36][CH2:35]2)=[CH:28][CH:27]=1>C1COCC1>[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][N:34]2[CH2:39][CH2:38][CH:37]([CH:40]=[O:41])[CH2:36][CH2:35]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8058HexaneHCID 7555721-[(4-fluorophenyl)methyl]-1H-1,3-benzodiazoleHCID 108695871-[2-(4-Methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl ester

Product 1

HCID 53767224[1-[2-(4-Methoxyphenyl)ethyl]-4-piperidinyl]methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred, -78° C., solution of 1-[(4-fluorophenyl)methyl]-1H-benzimidazol (1.13 g, 5.00×10-3 mole) and dry THF (12 ml) under argon was added a 2.5 molar hexane solution of n-butyl ithium (2.1 ml, 5.25×10-3 mole). After 15-20 minutes at -78° C., a solution of 1-[2-(4-methoxyphenyl)ethyl]-4-piperidinecarboxylic acid, methyl ester (1.39 g, 5.01×10-3 mole) and dry THF (6 ml) was added dropwise via syringe. After 5-10 minutes, the cooling bath was removed and the reaction was allowed to warm. After ca. 30 minutes, the reaction was quenched by the addition of saturated aqueous NH4Cl. The reaction was transferred to a separatory funnel where the aqueous mixture was extracted two times with ethyl acetate. The ethyl acetate extracts were combined, washed with saturated aqueous NaCl, and dried over anhydrous Na2SO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure affording a viscous oil. This was purified by a combination of flash chromatography (ethyl acetate) and crystallization (cyclohexane) affording 1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl][1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methanone as off white matted needles: 0.90 g (38%), m.p. 109°-111° C.

Workup

  1. waitAfter 5-10 minutes
  2. customthe cooling bath was removed
  3. temperatureto warm
  4. waitAfter ca. 30 minutes
  5. customthe reaction was quenched by the addition of saturated aqueous NH4Cl
  6. customThe reaction was transferred to a separatory funnel
  7. extractionwhere the aqueous mixture was extracted two times with ethyl acetate
  8. washwashed with saturated aqueous NaCl
  9. dry with materialdried over anhydrous Na2SO4
  10. customThe drying agent was removed by filtration
  11. customthe filtrate was evaporated at reduced pressure
  12. customaffording a viscous oil
  13. customThis was purified by a combination of flash chromatography (ethyl acetate) and crystallization (cyclohexane)

Sources & evidence

ORD record
ord-21da7227ebca418984c7e8df4b9248f5
Source dataset
uspto-grants-1990_03
Patent number
US04908372

Reaction notes

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