Water → 4-[4-[4-(cis-2,6-Dimethylmorpholin-4-yl)phenyl]piperazin-1-yl]benzoic acid ethyl ester

HRID 1816752Notes

Reaction equation

HRID 1816752 reaction equation
[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][N:4]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH2:3]1.[CH2:21]([O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28](F)=[CH:27][CH:26]=1)[CH3:22].C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O.ClCCl>[CH2:21]([O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28]([N:18]2[CH2:17][CH2:16][N:15]([C:12]3[CH:11]=[CH:10][C:9]([N:4]4[CH2:3][C@H:2]([CH3:1])[O:7][C@H:6]([CH3:8])[CH2:5]4)=[CH:14][CH:13]=3)[CH2:20][CH2:19]2)=[CH:27][CH:26]=1)[CH3:22]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium Carbonate2×HCID 67976Benzoic acid, 4-fluoro-, ethyl ester2×HCID 69677628cis-2,6-Dimethyl-4-(4-piperazinylphenyl)morpholine

Product 1

HCID 696777484-[4-[4-(cis-2,6-Dimethylmorpholin-4-yl)phenyl]piperazin-1-yl]benzoic acid ethyl esterYield 81.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of cis-2,6-dimethyl-4-(4-piperazinylphenyl)morpholine (2.00 g), 4-fluorobenzoic acid ethyl ester (1.43 g) and potassium carbonate (1.01 g) in dimethylsulfoxide (40 ml) was stirred for 8 hours at 150° C., during which period additional 4-fluorobenzoic acid ethyl ester (1.35 g) and potassium carbonate (1.0 g) was added to the mixture. The reaction mixture was added to a mixture of water and dichloromethane. The organic layer was taken and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (25:1 dichloromethane-methanol elution) to give 4-[4-[4-(cis-2,6-dimethylmorpholin-4-yl)phenyl]piperazin-1-yl]benzoic acid ethyl ester (2.5 g).

Workup

  1. additionwas added to the mixture
  2. dry with materialdried over magnesium sulfate
  3. filtrationThe magnesium sulfate was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (25:1 dichloromethane-methanol elution)

Sources & evidence

ORD record
ord-cdad8073772f4db6a2a501795a225214
Source dataset
uspto-grants-2005_04
Patent number
US06884868B1

Reaction notes

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