Iodine → 2-Chloro-5-fluoro-4-isopropyl-pyrimidine

HRID 1618966ノート

反応式

HRID 1618966 の反応式
[F:1][C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH:9]([Mg]Cl)([CH3:11])[CH3:10].C(N(CC)CC)C.II>COCCOC.O1CCCC1>[Cl:8][C:5]1[N:6]=[C:7]([CH:9]([CH3:11])[CH3:10])[C:2]([F:1])=[CH:3][N:4]=1

参加物

7

反応物 4

HCID 807IodineHCID 8471TriethylamineHCID 5834662-Chloro-5-fluoropyrimidineHCID 178418918HCID 178418918、化合物

生成物 1

HCID 583334102-Chloro-5-fluoro-4-isopropyl-pyrimidine収率 39%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
0 °C

実験手順

A solution of 5-fluoro-2-chloropyrimidine (5.00 g, 37.7 mmol) in 1,2-dimethoxyethane (25 mL) is treated with a solution of 2 M isopropyl magnesium chloride in tetrahydrofuran (28.3 mL, 56.6 mmol) while keeping the temperature below 15° C. The resulting solution is stirred for one hour under nitrogen and then cooled to 0° C. and treated drop wise with a solution of triethylamine (5.76 mL, 37.7 mmol) in tetrahydrofuran (5 mL). A solution of iodine (9.58 g, 37.7 mmol) in tetrahydrofuran (20 mL) is added. The reaction is quenched with water and saturated sodium bicarbonate and saturated sodium bisulfate are added. The mixture is extracted three times with ethyl acetate. The combined organic layers are dried over sodium sulfate and the solvent is removed under vacuum. The crude product is purified over silica gel with a 30 minute gradient, dichloromethane/hexanes (5 to 100%) to give the title compound (2.55 g, 39%). GC/MS (m/e): 174.

後処理

  1. customthe temperature below 15° C
  2. customThe reaction is quenched with water and saturated sodium bicarbonate and saturated sodium bisulfate
  3. additionare added
  4. extractionThe mixture is extracted three times with ethyl acetate
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. customthe solvent is removed under vacuum
  7. customThe crude product is purified over silica gel with a 30 minute gradient, dichloromethane/hexanes (5 to 100%)

出典と根拠

ORDレコード
ord-8dd7cbfd647e456dbdbbb44ee24cf71b
出典データセット
uspto-grants-2014_07
特許番号
US08772282B2

反応ノート

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