Potassium Phosphate, Tribasic → Tert-butyl 4-cyclopropylpyridin-3-ylcarbamate

HRID 705359ノート

反応式

HRID 705359 の反応式
I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:24]1(B(O)O)[CH2:26][CH2:25]1.F[B-](F)(F)F.C1([PH+](C2CCCCC2)C2CCCCC2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH:24]1([C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:26][CH2:25]1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 11710396Tricyclohexylphosphonium TetrafluoroborateHCID 15366413(4-Iodo-pyridin-3-YL)-carbamic acid tert-butyl ester

生成物 1

HCID 67981637Tert-butyl 4-cyclopropylpyridin-3-ylcarbamate収率 86.7%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

A pressure tube purged with nitrogen was charged with tert-butyl 4-iodopyridin-3-ylcarbamate (1.0 g, 3.12 mmol), potassium phosphate (2.393 g, 10.93 mmol), toluene (16 mL) and H2O (0.800 mL). The mixture was sparged with nitrogen for 20 minutes. Then cyclopropylboronic acid (0.349 g, 4.06 mmol), tricyclohexylphosphonium tetrafluoroborate (0.116 g, 0.312 mmol), and palladium(II) acetate (0.035 g, 0.156 mmol) were added, and the mixture was sparged with nitrogen for 15 minutes. The tube was closed with a pressure release valve top, and the mixture was heated at 100° C. for 20 hours. TLC (SiO2, 50% ethyl acetate/CH2Cl2) showed no starting material and a lower. Rf product. LCMS showed no starting material, and a large product peak, m/z 235. The reaction was cooled to room temperature, and the residue was taken up in ethyl acetate (100 mL), and washed with H2O (50 mL). The aqueous phase was re-extracted with ethyl acetate (50 mL), and the combined organic extracts were washed with brine (25 mL), dried over anhydrous MgSO4, filtered, and concentrated by rotary evaporation. The crude material was purified by SiO2 flash chromatography (2.5 cm×15 cm) eluting with CH2Cl2 to 6:4 ethyl acetate/CH2Cl2 to afford the product as a colorless viscous oil (634 mg).

後処理

  1. customA pressure tube purged with nitrogen
  2. customThe mixture was sparged with nitrogen for 20 minutes
  3. customthe mixture was sparged with nitrogen for 15 minutes
  4. customThe tube was closed with a pressure release valve top
  5. temperatureThe reaction was cooled to room temperature
  6. washwashed with H2O (50 mL)
  7. extractionThe aqueous phase was re-extracted with ethyl acetate (50 mL)
  8. washthe combined organic extracts were washed with brine (25 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated by rotary evaporation
  12. customThe crude material was purified by SiO2 flash chromatography (2.5 cm×15 cm)
  13. washeluting with CH2Cl2 to 6:4 ethyl acetate/CH2Cl2

出典と根拠

ORDレコード
ord-b09881def4f84113aef22e46ba2b9671
出典データセット
uspto-grants-2015_11
特許番号
US09173887B2

反応ノート

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