Potassium Phosphate, Tribasic → HCID 86703466, compound

HRID 1849610Notes

Reaction equation

HRID 1849610 reaction equation
Cl[C:2]1[C:3]([O:16][CH2:17][C:18]2([CH3:24])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9]C(C)(C)C)=[O:8].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:33]1(B(O)O)[CH2:35][CH2:34]1.F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH:33]1([C:2]2[C:3]([O:16][CH2:17][C:18]3([CH3:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([OH:9])=[O:8])[CH2:35][CH2:34]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703465HCID 86703465, compound

Product 1

HCID 86703466HCID 86703466, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 22272177Toluene waterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 5-chloro-2-fluoro-4-((1-methylcyclohexyl)methoxy)benzoate (1.63 g, 4.6 mmol) in toluene-water (v/v 20:1, 21 mL) was added tribasic potassium phosphate (4.37 g, 20.60 mmol), cyclopropylboronic acid (0.581 g, 6.80 mmol) and tricyclohexylphosphine tetrafluoroborate (0.168 g, 0.46 mmol). The mixture was sonicated for 5 minutes, and then sparged with nitrogen for 10 minutes; palladium acetate (0.053 g, 0.23 mmol) was added and the reaction mixture was heated to 100° C. and stirred for 16 hours under a nitrogen atmosphere. The reaction mixture was cooled to ambient temperature and poured into water. The aqueous layer was separated and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in anhydrous dichloromethane (8 mL) and trifluoroacetic acid (4 mL) was added. The mixture was stirred at ambient temperature for 3 hours and then concentrated in vacuo. The crude solid obtained was triturated with hexanes to provide the title compound (0.62 g, 44%): 1H NMR (300 MHz, DMSO-d6) δ 12.80 (br s, 1H), 7.33 (d, J=8.5 Hz, 1H), 6.92 (d, J=13.2 Hz, 1H), 3.79 (s, 2H), 2.06-1.96 (m, 1H), 1.48-1.17 (m, 10H), 1.04 (s, 3H), 0.92-0.86 (m, 2H), 0.61-0.56 (m, 2H).

Workup

  1. customThe mixture was sonicated for 5 minutes
  2. customsparged with nitrogen for 10 minutes
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (3×50 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in anhydrous dichloromethane (8 mL)
  11. additiontrifluoroacetic acid (4 mL) was added
  12. stirringThe mixture was stirred at ambient temperature for 3 hours
  13. concentrationconcentrated in vacuo
  14. customThe crude solid obtained
  15. customwas triturated with hexanes

Sources & evidence

ORD record
ord-377030e28c834edabbd5ffe7e9435768
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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