Cesium carbonate → 6-Cyclopropylmethoxy-5-(3-hydroxy-azetidin-1-yl)-pyridine-2-carboxylic acid

HRID 927473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 927473
[NH:1]1[CH2:4][CH:3]([OH:5])[CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:59]1[CH:60]=[CH:61][C:62]([C:70]([OH:72])=[O:71])=[N:63][C:64]=1[O:65][CH2:66][CH:67]1[CH2:69][CH2:68]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:67]1([CH2:66][O:65][C:64]2[N:63]=[C:62]([C:70]([OH:72])=[O:71])[CH:61]=[CH:60][C:59]=2[N:1]2[CH2:4][CH:3]([OH:5])[CH2:2]2)[CH2:68][CH2:69]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 15142903-HydroxyazetidineHCID 710875435-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid

Produkt 1

HCID 710877626-Cyclopropylmethoxy-5-(3-hydroxy-azetidin-1-yl)-pyridine-2-carboxylic acidAusbeute 36,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a mixture of azetidin-3-ol (CAN 45347-82-8, 200 mg, 3 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (CAS 98327-87-8, 114 mg, 0.185 mmol), tris(dibenzylideneacetone)dipalladium (CAS 51364-51-3, 85 mg, 0.1 mmol) and cesium carbonate (CAS 534-17-8, 1.8 mg, 5.55 mmol) in toluene (8 mL) under nitrogen atmosphere, was added a solution of 5-bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 9 d, 500 mg, 1.85 mmol). The reaction mixture was stirred overnight at 110° C. The reaction mixture was concentrated in vacuo and the residue dissolved in water and extracted with ethyl acetate (1×30 mL). The aqueous layer was adjusted to pH=2 by addition of 1 N hydrochloric acid, the resulting precipitate was collected by filtration, the solid was lyophilized. The crude product was purified by flash chromatography (silica gel, 50 g, 0% to 100% ethyl acetate in petroleum ether) to give the desired product (180 mg) as a yellow solid; MS (EI): m/e=265.2 [M+H]+.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in water
  3. extractionextracted with ethyl acetate (1×30 mL)
  4. additionThe aqueous layer was adjusted to pH=2 by addition of 1 N hydrochloric acid
  5. filtrationthe resulting precipitate was collected by filtration
  6. customThe crude product was purified by flash chromatography (silica gel, 50 g, 0% to 100% ethyl acetate in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-233cc2497f534309a1c06fdb0c127255
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290451B2

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