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

HRID 626897

반응식

HRID 626897 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 178419050HCID 178419050, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
80 °C

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-43e6a028560a4eb59ea6b00184185984
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309254B2

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