Water → 5-Chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(4-oxohexyloxy)nicotinonitrile

HRID 1020816

Reaktionsgleichung

Reaktionsgleichung von HRID 1020816
FC(F)(F)C([O:5][C:6]1([CH2:9][CH2:10][CH2:11][O:12][C:13]2[C:18]([C:19]#[N:20])=[CH:17][C:16]([Cl:21])=[C:15](Cl)[N:14]=2)[CH2:8][CH2:7]1)=O.[B:25]1([OH:35])[C:29]2[CH:30]=[CH:31][C:32]([OH:34])=[CH:33][C:28]=2[CH2:27][O:26]1.C([O-])([O-])=O.[Cs+].[Cs+].O>CS(C)=O.CCOC(C)=O>[Cl:21][C:16]1[C:15]([O:34][C:32]2[CH:31]=[CH:30][C:29]3[B:25]([OH:35])[O:26][CH2:27][C:28]=3[CH:33]=2)=[N:14][C:13]([O:12][CH2:11][CH2:10][CH2:9][C:6](=[O:5])[CH2:8][CH3:7])=[C:18]([CH:17]=1)[C:19]#[N:20]

Komponenten

7

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 579686991,3-Dihydro-1-hydroxy-2,1-benzoxaborol-5-olHCID 866617251-(3-(5,6-Dichloro-3-cyanopyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate

Produkt 1

HCID 580800305-Chloro-6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(4-oxohexyloxy)nicotinonitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a mixture of compound 1-(3-(5,6-dichloro-3-cyanopyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate (0.87 g, 2.3 mmol) and benzo[c][1,2]oxaborole-1,5(3H)-diol (0.36 g, 2.4 mmol) in DMSO was added Cs2CO3 (0.89 g, 2.7 mmol) at room temperature and the resulting mixture was stirred at 40° C. overnight. The mixture was then poured into cold water, diluted with EtOAc, the organic phase was separated and the aqueous phase was further extracted twice with EtOAc. The combined organic layers were washed with brine twice, dried over Na2SO4 and concentrated, the residue was purified by Prep-HPLC (column: Luna 300×50.0 mm, 10μ; liquid phase: [A-H2O; B—CH3CN] B %: 35%-62%, 23 min) to give the product D233 (105 mg) and D234 (112 mg), total yield 24%.

Aufarbeitung

  1. customthe organic phase was separated
  2. extractionthe aqueous phase was further extracted twice with EtOAc
  3. washThe combined organic layers were washed with brine twice
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by Prep-HPLC (column: Luna 300×50.0 mm, 10μ; liquid phase: [A-H2O; B—CH3CN] B %: 35%-62%, 23 min)
  7. customto give the product D233 (105 mg) and D234 (112 mg), total yield 24%

Quellen und Nachweise

ORD-Eintrag
ord-616d124f5c65419ca086c4a0634e36f5
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716478B2

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