Potassium Phosphate, Tribasic → HCID 86623909, compound

HRID 1666464Notes

Reaction equation

HRID 1666464 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=2)[CH:16]=1)[CH2:5][P:6](=[O:13])([O:10][CH2:11][CH3:12])[O:7][CH2:8][CH3:9].[CH:28]1(B(O)O)[CH2:30][CH2:29]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1>[CH:28]1([C:2]2[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][N:19]=3)[CH:16]=2)[CH2:5][P:6](=[O:13])([O:10][CH2:11][CH3:12])[O:7][CH2:8][CH3:9])[CH2:30][CH2:29]1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 86623908Diethyl 3-bromo-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylphosphonate

Product 1

HCID 86623909HCID 86623909, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of diethyl 3-bromo-5-(5-(trifluoromethyl)pyridin-2-yloxy)benzylphosphonate (0.93 g, 1.99 mmol) and cyclopropylboronic acid (0.204 g, 2.38 mmol) in THF (5.6 mL) was added potassium phosphate (1.27 g, 5.99 mmol). The mixture was degassed by purging with argon. PdCl2(dppf2 (162.2 mg, 0.198 mmol) and water (0.11 mL) were added to the reaction mixture and the mixture was degassed again. The reaction was heated at 50° C. for 1 h. The reaction mixture was concentrated and extracted with ethyl acetate three times. The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness. The residue was purified by silica gel column chromatography (20% ethyl acetate in hexane) to give the title compound (0.8 g, 94%). 1H NMR (500 MHz, CDCl3): δ 8.42 (s, 1H), 7.87 (d, J=8.5 Hz, 1H), 6.96 (d, J=9 Hz, 1H), 6.90 (s, 1H), 6.86 (s, 1H), 6.73 (s, 1H),), 4.02 (m, 4H), 3.14 (s, 1H), 3.10 (s, 1H), 1.87 (m, 1H), 1.24 (m, 6H), 0.96 (d, J=8.5 Hz, 2H), 0.69 (d, J=5 Hz, 2H); m/z (430.0, M+ H+).

Workup

  1. customThe mixture was degassed
  2. customby purging with argon
  3. additionPdCl2(dppf2 (162.2 mg, 0.198 mmol) and water (0.11 mL) were added to the reaction mixture
  4. customthe mixture was degassed again
  5. concentrationThe reaction mixture was concentrated
  6. extractionextracted with ethyl acetate three times
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. customevaporated to dryness
  10. customThe residue was purified by silica gel column chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-69232c2e6f6945179fb56030cc6c86cd
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…