Acetaminophen → N-[4-(4,6-Dichloro-pyrimidin-2-yloxy)-phenyl]-acetamide

HRID 225436

Reaction equation

HRID 225436 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[H-].[Na+].[Cl:14][C:15]1[CH:20]=[C:19]([Cl:21])[N:18]=[C:17](S(C)(=O)=O)[N:16]=1>C1COCC1.[NH4+].[Cl-].CCOC(C)=O>[Cl:14][C:15]1[CH:20]=[C:19]([Cl:21])[N:18]=[C:17]([O:11][C:8]2[CH:9]=[CH:10][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=2)[N:16]=1

Participants

7

Reactant 3

HCID 1983AcetaminophenHCID 24758Sodium hydrideHCID 2396854,6-Dichloro-2-(methylsulfonyl)pyrimidine

Product 1

HCID 57752793N-[4-(4,6-Dichloro-pyrimidin-2-yloxy)-phenyl]-acetamideYield 95.3%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A solution of 4-acetamidophenol (666 mg, 4.40 mmol) in anhydrous THF (40 ml), stirring at ambient temperature, was treated with a 60% dispersion of sodium hydride in mineral oil (176 mg, 4.40 mmol). The reaction mixture was then allowed to stir for 30 minutes at ambient temperature before 4,6-dichloro-2-methanesulfonyl-pyrimidine (1.0 g, 4.40 mmol) was added. The reaction was then allowed to stir for a further 3 hours before the reaction was diluted with saturated aqueous NH4Cl and EtOAc. The organic layer was separated, washed with saturated aqueous NaCl and dried over sodium sulfate then concentrated in vacuo. The residue was purified by column chromatography (Silica Gel, MeOH:CH2Cl2, 5:95) yield the title compound 1.25 g, (95%) as a solid. 1H-NMR (400 MHz, DMSO-d6): δ 2.06 (3 H, s), 7.18 (2 H, d, J=8.5 Hz), 7.62 (2 H, d, J=8.5 Hz), 10.05 (1 H, s), LC-MS: ES+=298.16, ES−=296.18).

Workup

  1. additionwas added
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous NaCl
  4. dry with materialdried over sodium sulfate
  5. concentrationthen concentrated in vacuo
  6. customThe residue was purified by column chromatography (Silica Gel, MeOH:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-c804fb4d8e134d36865990200ea5ae82
Source dataset
uspto-grants-2009_07
Patent number
US07557106B2

Linked notes

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