4-Aminophenol → HCID 58659435, compound

HRID 1993548Notes

Reaction equation

HRID 1993548 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[H][H].Cl[C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[N:17]=[CH:16][N:15]=1>O1CCOCC1>[F:21][C:20]([F:23])([F:22])[C:18]1[N:17]=[CH:16][N:15]=[C:14]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:19]=1

Participants

6

Reactant 4

HCID 4034-AminophenolHCID 24758Sodium hydrideHCID 115428814-Chloro-6-(trifluoromethyl)pyrimidineHCID 178418361HCID 178418361, compound

Product 1

HCID 58659435HCID 58659435, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
62.5 °C

Procedure

4-Amino-phenol (1.2 g, 10.9 mmol) is added in one portion to a suspension of NaH (60% free-flowing powder moistened with oil, 0.48 g, 12.0 mmol, 1.1 equiv) in dioxane abs. (18 mL), under an argon atmosphere. When hydrogen evolution subsides, a solution of 4-chloro-6-trifluoromethyl-pyrimidine (2.0 g, 10.9 mmol) in dioxane (2.0 mL) is added. The resulting dark mixture is heated to 60-65° C. (oil bath temperature) for 40 min, allowed to cool to rt, quenched by addition of MeOH and concentrated in vacuo. The residue is purified twice by silica gel (200 g) column chromatography (CH2Cl2/MeOH, 99/1, then 98/2) to afford the title compound as a white solid: ES-MS: 256.0 [M+H]+; single peak at tR=6.35 min (System 2); Rf=0.33 (CH2Cl2/MeOH, 98/2).

Workup

  1. temperatureto cool to rt
  2. customquenched by addition of MeOH
  3. concentrationconcentrated in vacuo
  4. customThe residue is purified twice by silica gel (200 g) column chromatography (CH2Cl2/MeOH, 99/1

Sources & evidence

ORD record
ord-c930df30df224e909209362f0faefed9
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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