Potassium Phosphate, Tribasic → HCID 86703466, Verbindung

HRID 1849610Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1849610
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

Komponenten

8

Edukt 4

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

Produkt 1

HCID 86703466HCID 86703466, VerbindungAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 22272177Toluene waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-377030e28c834edabbd5ffe7e9435768
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952169B2

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