Potassium Phosphate, Tribasic → 5-Bromo-2-cyclopropyl-3-methoxypyridine

HRID 39358

反応式

HRID 39358 の反応式
Br[C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([Br:10])=[CH:4][N:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:19]1([CH3:25])C=CC=C[CH:20]=1.O>CCOC(C)=O.[Na+].[Cl-]>[Br:10][C:5]1[CH:6]=[C:7]([O:8][CH3:9])[C:2]([CH:25]2[CH2:19][CH2:20]2)=[N:3][CH:4]=1

参加物

6

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 22272177Toluene waterHCID 467368252,5-Dibromo-3-Methoxypyridine

生成物 1

HCID 666173635-Bromo-2-cyclopropyl-3-methoxypyridine収率 70%

試薬・触媒・溶媒 2

HCID 5234Sodium Chloride溶媒HCID 8857Ethyl Acetate溶媒

実験手順

As shown in step 6-v of Scheme 6, Compound 1020 (3.6 g, 13.5 mmol), potassium cyclopropyl-trifluoro-boron (2.5 g, 16.9 mmol), and potassium phosphate (8.6 g, 40.5 mmol) were taken up in about 80 mL of a toluene/water mixture. The reaction mixture was flushed with nitrogen gas for 10 minutes and Pd(PPh3)4 (1.4 g, (1.21 mmol) was added. The reaction mixture was refluxed for 18 hours, resulting in a mixture of products by HPLC analysis. The reaction was cooled, diluted with EtOAc and saturated NaCl. The organics were separated, dried (MgSO4), and concentrated under reduced pressure to provide a solid, which was purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient) to give 5-bromo-2-cyclopropyl-3-methoxypyridine (Compound 1022, 0.54 g, 70% pure): ESMS (M+H) 227.9/229.9. This compound was used as is in subsequent reactions.

後処理

  1. customThe reaction mixture was flushed with nitrogen gas for 10 minutes
  2. additionPd(PPh3)4 (1.4 g, (1.21 mmol) was added
  3. temperatureThe reaction mixture was refluxed for 18 hours
  4. customresulting in a mixture of products by HPLC analysis
  5. temperatureThe reaction was cooled
  6. customThe organics were separated
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customto provide a solid, which
  10. customwas purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-5572f7d79e614a3186d3b1809bed68ec
出典データセット
uspto-grants-2013_09
特許番号
US08524906B2

関連ノート

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