Cesium carbonate → 6-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid methyl ester

HRID 631950

Reaktionsgleichung

Reaktionsgleichung von HRID 631950
[CH:1]1([B-](F)(F)F)[CH2:3][CH2:2]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:15][O:16][C:17]([C:19]1[CH:24]=[CH:23][C:22](Br)=[C:21]([Cl:26])[N:20]=1)=[O:18]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(PC12CC3CC(CC(C3)C1)C2)CCC>[CH3:15][O:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([CH:1]2[CH2:3][CH2:2]2)=[C:21]([Cl:26])[N:20]=1)=[O:18]

Komponenten

8

Edukt 3

HCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 46311197Methyl 5-bromo-6-chloropicolinate

Produkt 1

HCID 866747356-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid methyl esterAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 68995490Butyl-1-adamantylphosphineKatalysatorHCID 962WaterLösungsmittel2×HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a mixture of palladium(II)acetate (17.9 mg, 79.8 μmol), butyl-1-adamantylphosphine (42.9 mg, 120 μmol), potassium cyclopropyltrifluoroborate (597 mg, 4.03 mmol) and cesium carbonate (3.9 g, 12.0 mmol) under an argon atmosphere was added a solution of 5-bromo-6-chloro-pyridine-2-carboxylic acid methyl ester (CAN 1214353-79-3, 1 g, 3.99 mmol) in toluene (25.2 ml) and water (2.8 mL) under an argon atmosphere. The reaction mixture was heated to 100° C. for 20 h, diluted with water (17.5 ml), poured onto 100 ml ice/brine and extracted with i-PrOAc (2×100 mL). The combined extracts were dried over sodium sulfate and concentrated in vacuo to give a yellow liquid. This crude material was purified by column chromatography (70 g SiO2, n-heptane/i-PrOAc 0-10% over 120 min) to give the title compound (497 mg, 59%) as yellow solid, MS (EI): m/e=212.0 [M+H]+.

Aufarbeitung

  1. extractionextracted with i-PrOAc (2×100 mL)
  2. dry with materialThe combined extracts were dried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a yellow liquid
  5. customThis crude material was purified by column chromatography (70 g SiO2, n-heptane/i-PrOAc 0-10% over 120 min)

Quellen und Nachweise

ORD-Eintrag
ord-d7687936a2cf43aaa44a1bd9a7b59664
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321727B2

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