Cesium fluoride → Methyl 2-(6-aminopyridin-3-yloxy)-4-fluorobenzoate

HRID 1848866Notes

Reaction equation

HRID 1848866 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)O1.[F-].[Cs+].Br[C:20]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:21]=1[C:22]([O:24][CH3:25])=[O:23].C(COC)[O:32]C.CO>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[NH2:15][C:12]1[N:13]=[CH:14][C:9]([O:32][C:20]2[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:21]=2[C:22]([O:24][CH3:25])=[O:23])=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 7210837Methyl 2-bromo-4-fluorobenzoateHCID 86595564Dimethoxyethane methanol

Product 1

HCID 67226188Methyl 2-(6-aminopyridin-3-yloxy)-4-fluorobenzoate

Reagents, catalysts & solvents 1

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (1.039 g), CsF (1.956 g), bis(triphenylphosphine)palladium(II)dichloride (0.301 g), and methyl 2-bromo-4-fluorobenzoate (1.0 g) in 50 mL dimethoxyethane-methanol (1:1) was heated at 80° C. for 2.5 hours. The reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with brine, dried over MgSO4, filtered, ad concentrated. The residue was chromatographed on silica gel with 25-80% ethyl acetate in hexanes.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. washThe organic phase was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationad concentrated
  6. customThe residue was chromatographed on silica gel with 25-80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-44a72f0d8e2d437393ef32f7b527b284
Source dataset
uspto-grants-2015_02
Patent number
US08952157B2

Reaction notes

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