Hydrochloric Acid → (2-Chloro-4-fluorophenyl)(3-fluoro-4-(pyrimidin-5-yl)pyridin-2-yl)methanone

HRID 593756

反応式

HRID 593756 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1I.C([Mg]Cl)(C)C.[F:15][C:16]1[C:17]([C:28]#N)=[N:18][CH:19]=[CH:20][C:21]=1[C:22]1[CH:23]=[N:24][CH:25]=[N:26][CH:27]=1.Cl.[OH-:31].[Na+]>C1COCC1.C(Cl)Cl.O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:28]([C:17]1[C:16]([F:15])=[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[N:26][CH:27]=2)[CH:20]=[CH:19][N:18]=1)=[O:31]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27365592-Chloro-4-fluoro-1-iodobenzeneHCID 867304123-Fluoro-4-(pyrimidin-5-yl)picolinonitrileHCID 178418918HCID 178418918、化合物

生成物 1

HCID 86730413(2-Chloro-4-fluorophenyl)(3-fluoro-4-(pyrimidin-5-yl)pyridin-2-yl)methanone収率 7.44%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

To a solution of 2-chloro-4-fluoro-1-iodobenzene (0.307 g, 1.199 mmol) in THF (Volume: 1.622 ml) cooled to −10° C. was added isopropylmagnesium chloride, 2M in THF (0.699 ml, 1.399 mmol) in one portion. After 30 min, 3-fluoro-4-(pyrimidin-5-yl)picolinonitrile (0.200 g, 0.999 mmol) was added. The reaction mixture was stirred at −10° C. for 30 min, then allowed to warm to room temperature and stirred overnight. Water and ice were carefully added, followed by acidification with 6 M HCl. After stirring for 1 hr, CH2Cl2 was added and the pH was adjusted to 8.5 with aqueous 4 M NaOH. The layers were separated. The aqueous phase was extracted with CH2Cl2 (5×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford an orange residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (24 g column, 35 mL/min, 60-100% EtOAc in hexanes over 23 min, tr=9 min) gave the title compound (0.029 g, 0.074 mmol, 7.44% yield) as an orange solid.

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. stirringAfter stirring for 1 hr
  4. customThe layers were separated
  5. extractionThe aqueous phase was extracted with CH2Cl2 (5×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford an orange residue
  10. customto be chromatographed
  11. customPurification of the crude material by silica gel chromatography
  12. customan ISCO machine (24 g column, 35 mL/min, 60-100% EtOAc in hexanes over 23 min, tr=9 min)

出典と根拠

ORDレコード
ord-847bcca1244048718ccbfde654dafe0f
出典データセット
uspto-grants-2016_01
特許番号
US09242967B2

関連ノート

読み込み中…