4-Aminophenol → 4-(6-Fluoropyrimidin-4-yloxy)benzenamine

HRID 1993545ノート

反応式

HRID 1993545 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[H][H].[F:13][C:14]1[CH:19]=[C:18](F)[N:17]=[CH:16][N:15]=1>O1CCOCC1>[F:13][C:14]1[N:15]=[CH:16][N:17]=[C:18]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:19]=1

参加物

6

反応物 4

HCID 4034-AminophenolHCID 24758Sodium hydrideHCID 1377174,6-DifluoropyrimidineHCID 178418361HCID 178418361、化合物

生成物 1

HCID 586594294-(6-Fluoropyrimidin-4-yloxy)benzenamine

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒2 回

実験手順

4-Amino-phenol (0.135 g, 1.21 mmol) is added in one portion to a suspension of NaH (60% free-flowing powder moistened with oil, 58.2 mg, 1.45 mmol, 1.2 equiv) in dioxane abs. (1.4 mL), under an argon atmosphere. When hydrogen evolution subsides, a solution of 4,6-difluoro-pyrimidine (0.141 g, 1.21 mmol) in dioxane (0.4 mL) Is added. The resulting dark mixture is stirred for 1.5 h at rt, quenched by addition of MeOH (2 mL) and concentrated in vacuo. After addition of CH2Cl2, the resulting suspension is filtered and concentrated in vacuo. The residue is purified by silica gel column chromatography (CH2Cl2/Et2O, 90/10, then 85/15) to afford the title compound as a white solid: ES-MS: 204.0 [M+H]+; single peak at tR=4.96 min (System 2); Rf=0.30 (CH2Cl2/Et2O, 85/15).

後処理

  1. customquenched by addition of MeOH (2 mL)
  2. concentrationconcentrated in vacuo
  3. additionAfter addition of CH2Cl2
  4. filtrationthe resulting suspension is filtered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel column chromatography (CH2Cl2/Et2O, 90/10

出典と根拠

ORDレコード
ord-d938ce83a85d4291b07a4f2181d2b472
出典データセット
uspto-grants-2010_01
特許番号
US07652022B2

反応ノート

読み込み中…