Water → N-(1-benzyl-4-piperidyl)-N-isopropyl-4-fluorobenzamide

HRID 1493872Notes

Reaction equation

HRID 1493872 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.O.Cl.Cl.[CH2:14]([N:21]1[CH2:26][CH2:25][CH:24]([NH:27][CH:28]([CH3:30])[CH3:29])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C.O>ClC(Cl)Cl>[CH2:14]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]([CH:28]([CH3:30])[CH3:29])[C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:23][CH2:22]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 678794-Fluorobenzoyl chlorideHCID 198294211-Benzyl-4-isopropylaminopiperidine dihydrochloride hydrate

Product 1

HCID 19829431N-(1-benzyl-4-piperidyl)-N-isopropyl-4-fluorobenzamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
20 °C

Procedure

4-fluorobenzoic acid chloride (3.7 cc) is added to a solution of 1-benzyl-4-isopropylaminopiperidine dihydrochloride hydrate (3.83 g) and triethylamine (15 cc) in trichloromethane (50 cc). After 6 hours' stirring at 20° C., water (50 cc) is poured in and the mixture is left to stand for 16 hours. Settling is allowed to take place and the aqueous phase is extracted with trichloromethane (50 cc). The organic phases are washed with water (50 cc), then dried over magnesium sulphate and concentrated to dryness under reduced pressure (5.2 kPa). The oil obtained is chromatographed on a column 4 cm in diameter containing silica gel (200 g), eluting first with a dichloromethane/ethanol mixture (95:5 by volume) (1400 cc) and collecting 60-cc fractions. The fractions between 480 and 1980 cc are concentrated to dryness to give an ocher solid which is recrystallized in a diisopropylether/ethanol mixture (95:5 by volume) to obtain N-(1-benzyl-4-piperidyl)-N-isopropyl-4-fluorobenzamide (1.2 g) in the form of a white solid, m.p. 98° C.

Workup

  1. waitis left
  2. waitto stand for 16 hours
  3. extractionthe aqueous phase is extracted with trichloromethane (50 cc)
  4. washThe organic phases are washed with water (50 cc)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated to dryness under reduced pressure (5.2 kPa)
  7. customThe oil obtained
  8. customis chromatographed on a column 4 cm in diameter
  9. additioncontaining silica gel (200 g)
  10. washeluting first with a dichloromethane/ethanol mixture (95:5 by volume) (1400 cc)
  11. customcollecting 60-cc fractions
  12. concentrationThe fractions between 480 and 1980 cc are concentrated to dryness
  13. customto give an ocher solid which
  14. customis recrystallized in a diisopropylether/ethanol mixture (95:5 by volume)

Sources & evidence

ORD record
ord-6618ed9ed24547b5a351e25c6190f55c
Source dataset
uspto-grants-1991_06
Patent number
US05025013

Reaction notes

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