Sodium Carbonate → 2-Chloro-4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidine

HRID 626897

反応式

HRID 626897 の反応式
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH3:9])[N:3]=1.[CH2:10]([O:12][C:13]1[CH:14]=[CH:15][C:16]([F:22])=[C:17](B(O)O)[CH:18]=1)[CH3:11].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:15]2[CH:14]=[C:13]([O:12][CH2:10][CH3:11])[CH:18]=[CH:17][C:16]=2[F:22])[CH:5]=[C:4]([CH3:9])[N:3]=1

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 794712,4-Dichloro-6-methylpyrimidineHCID 162174685-Ethoxy-2-fluorophenylboronic Acid (contains varying amounts of Anhydride)

生成物 1

HCID 900153922-Chloro-4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidine収率 96.6%

試薬・触媒・溶媒 3

HCID 178419050HCID 178419050、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

To a solution of 2,4-dichloro-6-methyl-pyrimidine (2.66 g, 16.31 mmol) and (5-ethoxy-2-fluoro-phenyl)boronic acid (2 g, 10.87 mmol) in 1,2-dimethoxyethane (25 mL) and water (15 mL) was added sodium carbonate (3.46 g, 32.62 mmol). This was degassed with nitrogen for 5 minutes. Bis(triphenylphosphine)palladium (II) dichloride (0.38 g, 0.54 mmol) was then added and the reaction was heated to 80° C. overnight. The solvent was evaporated and the residue was partitioned between water (300 mL) and EtOAc (300 mL). The organics were washed with brine (100 mL), dried over MgSO4 and concentrated in vacuo to afford a yellow oil. The material was purified using a Biotage SP4 eluting with 0 to 30% i-hexane/EtOAc and the product containing fractions were collected and the solvent evaporated to give a colourless solid (2.8 g) mainly 2-chloro-4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidine (D16)

後処理

  1. customThis was degassed with nitrogen for 5 minutes
  2. customThe solvent was evaporated
  3. customthe residue was partitioned between water (300 mL) and EtOAc (300 mL)
  4. washThe organics were washed with brine (100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow oil
  8. customThe material was purified
  9. washeluting with 0 to 30% i-hexane/EtOAc
  10. additionthe product containing fractions
  11. customwere collected
  12. customthe solvent evaporated

出典と根拠

ORDレコード
ord-43e6a028560a4eb59ea6b00184185984
出典データセット
uspto-grants-2016_04
特許番号
US09309254B2

関連ノート

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