Hydrochloric Acid → Methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)isonicotinate hydrochloride

HRID 1963219ノート

反応式

HRID 1963219 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>CO.CC(OC)(C)C.Cl[Pd]Cl>[ClH:1].[F:12][C:13]1[CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=[CH:15][C:14]=1[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 164141452-Fluoro-4-(trifluoromethyl)benzeneboronic acid

生成物 1

HCID 66732338Methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)isonicotinate hydrochloride収率 99%

試薬・触媒・溶媒 3

HCID 24290Palladium Chloride触媒HCID 887Methanol溶媒HCID 15413tert-Butyl methyl ether溶媒2 回

反応条件

温度
100 °C

実験手順

Methyl 2-chloroisonicotinate (2.8 g, 16.32 mmol), 2-fluoro-4-(trifluoromethyl)phenylboronic acid (5.09 g, 24.48 mmol), potassium carbonate (1.692 g, 12.24 mmol) and PdCl2 (dppf) (0.354 g, 0.49 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a dark-orange solid. The solid was dissolved in MTBE and stirred for 15 minutes, then filtered. The orange MTBE layer was treated with hydrogen chloride (4 M in dioxane, 4.08 mL, 16.32 mmol) and stirred for 1 h at room temperature. The precipitate was collected by filtration. Methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)isonicotinate hydrochloride (5.4 g, 99%) was isolated as a slightly orange solid. MS m/z 300 (M+H)+

後処理

  1. customseparate 20 mL microwave vials
  2. customThe vials were capped
  3. additionWater and DCM were added
  4. customthe phases were separated
  5. extractionThe water phase (pH 9) was extracted with DCM
  6. washthe combined organic phase washed with brine
  7. customevaporated
  8. customto yield a dark-orange solid
  9. filtrationfiltered
  10. stirringstirred for 1 h at room temperature
  11. filtrationThe precipitate was collected by filtration

出典と根拠

ORDレコード
ord-766f86eed66f479ea83c4d4c0eb803be
出典データセット
uspto-grants-2013_04
特許番号
US08415378B2

反応ノート

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