Ethyl Acetate → O-tert-butyl N-(4-fluorobenzyl)-N-(1-acetylpiperidin-4-yl)carbamate

HRID 49794Notes

Reaction equation

HRID 49794 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[Na+].[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1.C(OCC)(=O)C>CN(C)C=O.O>[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][N:10]([CH:7]2[CH2:8][CH2:9][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]2)[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 22741830tert-Butyl (1-acetylpiperidin-4-yl)carbamate

Product 1

HCID 9841338O-tert-butyl N-(4-fluorobenzyl)-N-(1-acetylpiperidin-4-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of O-tert-butyl (1-acetylpiperidin-4-yl)carbamate (0.97 g) in N,N-dimethylformamide (10 ml) was added 60% sodium hydride (0.18 g) at ambient temperature. After stirring for 40 minutes, 4-fluorobenzyl bromide (0.6 ml) was added to the reaction mixture. After additional stirring for 4 hours, the reaction mixture was poured into a mixture of ethyl acetate (50 ml) and water (10 ml). An organic phase was separated and washed with water and brine. After drying with magnesium sulfate, the solvents were removed under reduced pressure. A residue was purified by column chromatography (silica gel 100 ml, toluene:ethyl acetate=1:1 to 1:2). After crystallization from diisopropyl ether and n-hexane, O-tert-butyl N-(4-fluorobenzyl)-N-(1-acetylpiperidin-4-yl)carbamate (922 mg) was obtained.

Workup

  1. stirringAfter additional stirring for 4 hours
  2. customAn organic phase was separated
  3. washwashed with water and brine
  4. dry with materialAfter drying with magnesium sulfate
  5. customthe solvents were removed under reduced pressure
  6. customA residue was purified by column chromatography (silica gel 100 ml, toluene:ethyl acetate=1:1 to 1:2)
  7. customAfter crystallization from diisopropyl ether and n-hexane

Sources & evidence

ORD record
ord-110ac8c91a2f40a1a3df0e7c232ab79c
Source dataset
uspto-grants-2004_03
Patent number
US06710043B1

Reaction notes

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