1-Chloro-4-(chloromethyl)benzene → HCID 53361024, compound

HRID 1023372Notes

Reaction equation

HRID 1023372 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4](/[CH:24]=[CH:25]/[C:26]([N:28]2[CH2:33][CH2:32][N:31]([CH2:34][C:35]3[CH:40]=[CH:39][C:38]([CH2:41][CH2:42][OH:43])=[CH:37][CH:36]=3)[CH2:30][CH2:29]2)=[O:27])[CH:5]=[C:6]([CH3:23])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:11][N:10]=1.[H-].[Na+].[Cl:46][C:47]1[CH:54]=[CH:53][C:50]([CH2:51]Cl)=[CH:49][CH:48]=1.[NH4+].[Cl-]>CN(C=O)C>[Cl:46][C:47]1[CH:54]=[CH:53][C:50]([CH2:51][O:43][CH2:42][CH2:41][C:38]2[CH:37]=[CH:36][C:35]([CH2:34][N:31]3[CH2:32][CH2:33][N:28]([C:26](=[O:27])/[CH:25]=[CH:24]/[C:4]4[CH:3]=[C:2]([CH3:1])[C:7]([O:8][C:9]5[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]6[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=6)=[CH:11][N:10]=5)=[C:6]([CH3:23])[CH:5]=4)[CH2:29][CH2:30]3)=[CH:40][CH:39]=2)=[CH:49][CH:48]=1

Participants

6

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67327003HCID 67327003, compound

Product 1

HCID 53361024HCID 53361024, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a DMF (5 mL) solution of (E)-3-(3,5-dimethyl-4-{[5-(pyridin-4-ylmethoxy)-pyridin-2-yl]oxy}phenyl)-1-{4-[4-(2-hydroxyethyl)benzyl]piperazin-1-yl}prop-2-en-1-one (400 mg) was added NaH (35.9 mg, 60% in mineral oil) at 0° C., then the resultant mixture was stirred for 1 hour. To the mixture was added 4-chlorobenzyl chloride (0.093 mL) at 0° C., then the resultant mixture was stirred at room temperature for 3 hours. The mixture was poured into saturated aqueous NH4Cl, and extracted with AcOEt. The organic layer was washed with H2O and saturated aqueous NaCl, dried over anhydrous Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/1 to 1/0 and then AcOEt/MeOH=4/1) to afford (E)-1-[4-(4-{2-[(4-chlorobenzyl)oxy]ethyl}benzyl)piperazin-1-yl]-3-(3,5-dimethyl-4-{[5-(pyridin-4-ylmethoxy)pyridin-2-yl]oxy}phenyl)prop-2-en-1-one as a pale yellow amorphous powder (91 mg).

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with H2O and saturated aqueous NaCl
  3. dry with materialdried over anhydrous Na2SO4
  4. customevaporated
  5. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=1/1 to 1/0

Sources & evidence

ORD record
ord-d8efa4033ea84da2aefb566a952acd55
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

Loading…