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

HRID 2284500Notes

Reaction equation

HRID 2284500 reaction equation
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]

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

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%.

Workup

  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%

Sources & evidence

ORD record
ord-d31eba3aeda54c95ac810487220e715c
Source dataset
uspto-grants-2015_09
Patent number
US09145429B2

Reaction notes

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