Hydrochloric Acid → 5-Cyclopropyl-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid

HRID 624948Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 624948
Br[C:2]1[CH:3]=[CH:4][C:5]([C:17]([OH:19])=[O:18])=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12].[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>C1(C)C=CC=CC=1.O.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH:20]1([C:2]2[CH:3]=[CH:4][C:5]([C:17]([OH:19])=[O:18])=[N:6][C:7]=2[O:8][CH2:9][C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])[CH2:22][CH2:21]1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 866747855-Bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid

Produkt 1

HCID 866747875-Cyclopropyl-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acidAusbeute 76,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 75806TricyclohexylphosphineKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 22272177Toluene waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 5-bromo-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid (501 mg, 1.43 mmol), cyclopropylboronic acid (CAN 411235-57-9, 184 mg, 2.15 mmol), palladium diacetate (CAN 3375-31-3, 16.1 mg, 71.6 μmol), tricyclohexylphosphine (CAN 2622-14-2, 8.03 mg, 28.6 μmol) and potassium phosphate (1.06 g, 5.01 mmol) in toluene/water (20/1 v/v, 10.5 mL) was stirred at 100° C. for 22 hours. After cooling the mixture was poured into ice-water (80 mL). 2 M Hydrochloric acid (25 mL) was added and the mixture was extracted with TBME, organic layers were washed twice with water, pooled, dried with Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, ethyl acetate/n-heptane gradient) to give the title compound (340 mg, 76%) as off-white solid; LC-MS (UV peak area, ESI) 96.6%, 310.0513 [M−H−].

Aufarbeitung

  1. temperatureAfter cooling the mixture
  2. extractionthe mixture was extracted with TBME, organic layers
  3. washwere washed twice with water
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, ethyl acetate/n-heptane gradient)

Quellen und Nachweise

ORD-Eintrag
ord-d2d8320358524fae82af8d903cd1a0e9
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303012B2

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