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

HRID 2167857Notes

Reaction equation

HRID 2167857 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

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-3db7aa92e34b46abad11aad9811433cb
Source dataset
uspto-grants-2015_06
Patent number
US09045441B2

Reaction notes

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