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

HRID 705359Notes

Reaction equation

HRID 705359 reaction equation
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

Participants

8

Reactant 4

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

Product 1

HCID 67981637Tert-butyl 4-cyclopropylpyridin-3-ylcarbamateYield 86.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b09881def4f84113aef22e46ba2b9671
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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