N,N-Dimethylglycine → Methyl 3-(6-aminopyridin-3-yloxy)benzoate

HRID 1684936Notes

Reaction equation

HRID 1684936 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[OH:9][C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=1)[C:13]([O:15][CH3:16])=[O:14].CN(C)CC(O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I>[NH2:8][C:5]1[N:6]=[CH:7][C:2]([O:9][C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][CH:19]=2)[C:13]([O:15][CH3:16])=[O:14])=[CH:3][CH:4]=1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 706222-Amino-5-bromopyridineHCID 88068Methyl 3-Hydroxybenzoate

Product 1

HCID 67263263Methyl 3-(6-aminopyridin-3-yloxy)benzoateYield 51.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A procedure described by D. Ma and Q. Cai (Org. Lett. 3799, 2003) was followed. To a solution of 5-bromopyridin-2-amine (346 mg, 2 mmol) in dioxane (10 mL) were added methyl 3-hydroxybenzoate (400 mg, 2.6 mmol), CuI (50 mg), N,N-dimethylglycine (60 mg) and Cs2CO3 (1.0 g). The resulting mixture was heated to 120° C. for 5 h, then cooled and partitioned between water and dichloromethane. The organic layer was separated, dried, and concentrated. The residue was purified by silica gel column eluting with ethyl acetate in dichloromethane (1:1) to obtain methyl 3-(6-aminopyridin-3-yloxy)benzoate (250 mg, 50%) as an oil. LC/MS; (M+H)+=245.

Workup

  1. temperaturecooled
  2. custompartitioned between water and dichloromethane
  3. customThe organic layer was separated
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column
  7. washeluting with ethyl acetate in dichloromethane (1:1)

Sources & evidence

ORD record
ord-1a2cae8af1bd4feda962544efec2b2ed
Source dataset
uspto-grants-2012_04
Patent number
US08148361B2

Reaction notes

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