Potassium Carbonate → (E)-3-[3-chloro-4-({5-[(3-fluoro-4-methylbenzyl)oxy]pyridin-2-yl}oxy)-5-methylphenyl]-1-(4-{4-[2-(4-chlorophenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one

HRID 1023371Notes

Reaction equation

HRID 1023371 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:17]=[CH:18]/[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][O:36][C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=4)=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)=[O:20])[CH:5]=[C:6]([CH3:16])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][N:10]=1.[F:44][C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][C:52]=1[CH3:53])[CH2:48]Br.C([O-])([O-])=O.[K+].[K+]>O>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:17]=[CH:18]/[C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][O:36][C:37]4[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=4)=[CH:30][CH:29]=3)[CH2:23][CH2:22]2)=[O:20])[CH:5]=[C:6]([CH3:16])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:48][C:47]2[CH:50]=[CH:51][C:52]([CH3:53])=[C:45]([F:44])[CH:46]=2)=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27746033-Fluoro-4-methylbenzyl bromideHCID 67327212(E)-3-{3-chloro-4-[(5-hydroxypyridin-2-yl)oxy]-5-methyl-phenyl}-1-(4-{4-[2-(4-chlorophenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one

Product 1

HCID 53361033(E)-3-[3-chloro-4-({5-[(3-fluoro-4-methylbenzyl)oxy]pyridin-2-yl}oxy)-5-methylphenyl]-1-(4-{4-[2-(4-chlorophenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (E)-3-{3-chloro-4-[(5-hydroxypyridin-2-yl)oxy]-5-methyl-phenyl}-1-(4-{4-[2-(4-chlorophenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one (400 mg) was added 3-fluoro-4-methylbenzyl bromide (144 mg) and K2CO3 (134 mg) at room temperature, then the reaction mixture was stirred for 4 hours. The reaction mixture was diluted with H2O and extracted with AcOEt. The organic layer was washed with water and saturated aqueous NaCl, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (AcOEt) to afford (E)-3-[3-chloro-4-({5-[(3-fluoro-4-methylbenzyl)oxy]pyridin-2-yl}oxy)-5-methylphenyl]-1-(4-{4-[2-(4-chlorophenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one as a colorless amorphous (430 mg).

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with water and saturated aqueous NaCl
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (AcOEt)

Sources & evidence

ORD record
ord-60268068e5234e4086e3145a1c770635
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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