Phenol → HCID 58248800, compound

HRID 2040401Notes

Reaction equation

HRID 2040401 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:17]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=4)[N:15]=[C:14]3[CH2:25][O:26][CH2:27][CH3:28])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1C=CC(S(O[CH2:48][C@@H:49]2[O:51][CH2:50]2)(=O)=O)=CC=1.C1(O)C=CC=CC=1>CN(C=O)C>[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[CH:17]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([O:24][CH2:48][C@H:49]5[CH2:50][O:51]5)=[CH:20][CH:19]=4)[N:15]=[C:14]3[CH2:25][O:26][CH2:27][CH3:28])=[CH:11][CH:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 10796Cesium carbonateHCID 154187Glycidyl tosylate, (R)-HCID 58248798HCID 58248798, compound

Product 1

HCID 58248800HCID 58248800, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 4-{1-[4-(4-chloro-phenoxy)-phenyl]-2-ethoxymethyl-1H-imidazol-4-yl}-phenol (0.21 g, 0.5 mmol, 1.0 eq.) and Cs2CO3 (0.49 g, 1.5 mmol, 3.0 eq.) in DMF (2 mL) was stirred and preheated to 80° C. The reaction mixture was then treated with a solution of (2R)-(−)-glycidyl tosylate (0.17 g, 0.75 mmol, 1.5 eq.) in 1 mL of DMF dropwise, and further stirred at 80° C. for ˜30 min following completion of the addition. Analysis of the reaction by TLC and LC/MS showed that the starting phenol had been consumed and the desired alkylated-phenol was the major product. The reaction was then cooled and diluted with EtOAc and washed with brine. The organic phase was dried with Na2SO4 and evaporated in vacuo. The crude alkylated-phenol was then purified by flash column chromatography over silica gel (EtOAc/hexanes ˜1:3).

Workup

  1. custompreheated to 80° C
  2. stirringfurther stirred at 80° C. for ˜30 min
  3. additioncompletion of the addition
  4. customAnalysis of the reaction by TLC and LC/MS
  5. customhad been consumed
  6. temperatureThe reaction was then cooled
  7. additiondiluted with EtOAc
  8. washwashed with brine
  9. dry with materialThe organic phase was dried with Na2SO4
  10. customevaporated in vacuo
  11. customThe crude alkylated-phenol was then purified by flash column chromatography over silica gel (EtOAc/hexanes ˜1:3)

Sources & evidence

ORD record
ord-fbbd7f25219e47a987defcbc6b9ff849
Source dataset
uspto-grants-2013_11
Patent number
US08580833B2

Reaction notes

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