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Cesium carbonate → 4-Benzyl-2-[3-chloro-4-(2,6-dichloro-benzyloxy)-phenyl]-morpholine

HRID 920545
Notes
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Reaction equation

HRID 920545 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([Cl:21])[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:22][C:23]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:24]=1[CH2:25]Br.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:25][C:24]3[C:23]([Cl:22])=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:31])=[C:16]([Cl:21])[CH:15]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 301591-Bromomethyl-2,6-dichlorobenzeneHCID 666540724-(4-Benzyl-morpholin-2-yl)-2-chloro-phenol

Product 1

HCID 670325214-Benzyl-2-[3-chloro-4-(2,6-dichloro-benzyloxy)-phenyl]-morpholineYield 102.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(4-benzyl-morpholin-2-yl)-2-chloro-phenol (0.50 g; 1.56 mmol), 2,6-dichlorobenzyl bromide (0.39 g; 1.64 mmol) and Cs2CO3 (2.55 g; 7.82 mmol) in CH3CN (20 mL) was heated under reflux overnight. After cooling to RT the resulting mixture was partitioned between EtOAc and water. The layers were separated and the organic layer, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, CH2Cl2:MeOH 98:2) to afford 4-benzyl-2-[3-chloro-4-(2,6-dichloro-benzyloxy)-phenyl]-morpholine (0.74 g)

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. customwas partitioned between EtOAc and water
  4. customThe layers were separated
  5. dry with materialthe organic layer, dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, CH2Cl2:MeOH 98:2)

Sources & evidence

ORD record
ord-96f1fa474f904cc498901d23f01e07b4
Source dataset
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09273017B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes