Cesium fluoride → Methyl 2-amino-5-methyl-4-(trifluoromethyl)benzoate

HRID 507027ノート

反応式

HRID 507027 の反応式
[F-].[Cs+].[CH3:3]B(O)O.[NH2:7][C:8]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[C:15](I)=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11]>O1CCOCC1>[NH2:7][C:8]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[C:15]([CH3:3])=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11]

参加物

5

反応物 3

HCID 25953Cesium fluorideHCID 139377Methylboronic AcidHCID 53436880Methyl 2-amino-5-iodo-4-(trifluoromethyl)benzoate

生成物 1

HCID 53436881Methyl 2-amino-5-methyl-4-(trifluoromethyl)benzoate収率 92%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

Add cesium fluoride (184.3 g, 1.21 mol), methyl boronic acid (63.7 g, 1.05 mol, 3 mol equiv.) and bis(diphenylphosphinoferrocene)palladium(II) chloride (27.83 g, 35.1 mmol) to a solution of methyl 2-amino-5-iodo-4-trifluoromethylbenzoate (121 g, 351 mmol) in anhydrous 1,4-dioxane (2.5 L) at room temperature under an atmosphere of nitrogen and heat the mixture at 80° C. for 3 h. Allow the mixture to cool to room temperature then partition between ethyl acetate (2.5 L) and water (2.5 L) and filter through a pad of Celite® to remove the fine black suspension. Extract the aqueous phase with ethyl acetate (2×100 mL) and wash the combined organic extracts with brine (1 L). Dry over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure at 45° C. to give a red oil. Purify the residue by column chromatography on silica gel, eluting with isohexane/ethyl acetate (9:1), to give the title compound as a pale yellow crystalline solid (75.25 g, 92%). 1H NMR (300 MHz, CDCl3) δ 7.73 (s, 1H), 6.93 (s, 1H), 5.70 (s, 2H), 3.90 (s, 3H), 2.33 (s, 3H).

後処理

  1. temperatureAllow the mixture to cool to room temperature
  2. customthen partition between ethyl acetate (2.5 L) and water (2.5 L)
  3. filtrationfilter through a pad of Celite®
  4. customto remove the fine black suspension
  5. extractionExtract the aqueous phase with ethyl acetate (2×100 mL)
  6. washwash the combined organic extracts with brine (1 L)
  7. dry with materialDry over anhydrous magnesium sulfate
  8. filtrationfilter
  9. customremove the solvent under reduced pressure at 45° C.
  10. customto give a red oil
  11. customPurify the residue by column chromatography on silica gel
  12. washeluting with isohexane/ethyl acetate (9:1)

出典と根拠

ORDレコード
ord-a9b6670863474ba291a9ab6ec2088043
出典データセット
uspto-grants-2010_08
特許番号
US07786108B2

反応ノート

読み込み中…