4-Aminophenol → [4-(4-Amino-phenoxy)-pyridin-2-yl]pyrrolidin-1-yl-methanone

HRID 1993536Notes

Reaction equation

HRID 1993536 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Cl[C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])[CH:11]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])[CH:11]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 4034-AminophenolHCID 11430Potassium CarbonateHCID 106799924-Chloro-2-(pyrrolidine-1-carbonyl)pyridine

Product 1

HCID 59134565[4-(4-Amino-phenoxy)-pyridin-2-yl]pyrrolidin-1-yl-methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Aminophenol (122 mg, 1.12 mmol) is dissolved in DMF (3 ml) and treated with potassium-tert-butylate (131 mg, 1.16 mmol) at rt. The reaction mixture is stirred for 2 h to give a brown suspension. (4-Chloro-pyridin-2-yl)-pyrrolidin-1-yl-methanone (Stage 101.1; 236 mg, 1.12 mmol) and K2CO3 (82 mg, 0.59 mmol) are added. The reaction mixture is then stirred for 12 h at 80° C. It Is allowed to cool to rt again and the solvent is removed in vacuo. The residual brown oil is taken up in ethyl acetate and washed with brine. The organic layer is dried over MgSO4, concentrated and the residual crude product is purified by flash chromatography (SiO2; gradient CH2Cl2/MeOH 99:1 to 92:8) to give the title compound as a slightly brown solid: C16H17N3O2: M+=284.2.

Workup

  1. customto give a brown suspension
  2. stirringThe reaction mixture is then stirred for 12 h at 80° C
  3. customthe solvent is removed in vacuo
  4. washwashed with brine
  5. dry with materialThe organic layer is dried over MgSO4
  6. concentrationconcentrated
  7. customthe residual crude product is purified by flash chromatography (SiO2; gradient CH2Cl2/MeOH 99:1 to 92:8)

Sources & evidence

ORD record
ord-90f4d18101d641ee895a519897a35edd
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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