p-Xylyl bromide → HCID 53361086, compound

HRID 1023370Notes

Reaction equation

HRID 1023370 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]([CH3:43])=[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.[CH3:44][C:45]1[CH:52]=[CH:51][C:48]([CH2:49]Br)=[CH:47][CH:46]=1.[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4](/[CH:17]=[CH:18]/[C:19]([N:21]2[CH2:22][CH2:23][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]([CH3:43])=[CH:39][CH:38]=4)=[CH:30][CH:29]=3)[CH2:25][CH2:26]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][CH2:44][C:45]2[CH:52]=[CH:51][C:48]([CH3:49])=[CH:47][CH:46]=2)=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 7721p-Xylyl bromideHCID 24758Sodium hydrideHCID 67354960HCID 67354960, compound

Product 1

HCID 53361086HCID 53361086, compoundYield 85.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a DMF (5 mL) solution of (E)-3-{3-chloro-4-[(5-hydroxypyridin-2-yl)oxy]-5-methylphenyl}-1-(4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one (479 mg) and 4-methylbenzyl bromide (155 mg) was added sodium hydride (60% w/w in oil, 42 mg) at 0° C., and stirred for 1 hour. The reaction mixture was quenched by addition of saturated aqueous NH4Cl (10 mL), and extracted with AcOEt. The organic layer was washed with water, saturated aqueous NaCl, dried over anhydrous Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (AcOEt/MeOH=1/0 to 9/1) to afford (E)-3-[3-chloro-5-methyl-4-({5-[(4-methylbenzyl)oxy]pyridin-2-yl}oxy)phenyl]-1-(4-{4-[2-(4-methylphenoxy)ethyl]benzyl}piperazin-1-yl)prop-2-en-1-one (480 mg).

Workup

  1. customThe reaction mixture was quenched by addition of saturated aqueous NH4Cl (10 mL)
  2. extractionextracted with AcOEt
  3. washThe organic layer was washed with water, saturated aqueous NaCl
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography (AcOEt/MeOH=1/0 to 9/1)

Sources & evidence

ORD record
ord-ff20e95d134441d694731fc38d092e44
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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