Cesium carbonate → Methyl 2-[(2-methoxyethoxy)methoxy]-3-(5-methoxypyridin-2-ylamino)benzoate

HRID 912430Notes

Reaction equation

HRID 912430 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH2:10])[C:5]=1[O:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17].Cl[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=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+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:17][O:16][CH2:15][CH2:14][O:13][CH2:12][O:11][C:5]1[C:6]([NH:10][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=2)=[CH:7][CH:8]=[CH:9][C:4]=1[C:3]([O:2][CH3:1])=[O:18]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 151690002-Chloro-5-methoxypyridineHCID 582228163-Amino-2-((2-methoxyethoxy)methoxy)benzoic acid methyl ester

Product 1

HCID 67410020Methyl 2-[(2-methoxyethoxy)methoxy]-3-(5-methoxypyridin-2-ylamino)benzoateYield 68%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-amino-2-((2-methoxyethoxy)methoxy)benzoic acid methyl ester 1.25 g (4.9 mmol) of step 2 in 1,4-dioxane 10 mL were added 2-chloro-5-methoxypyridine 0.70 g (4.9 mmol), Pd(OAc)2 0.11 g (0.49 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl 0.31 g (0.49 mmol) and Cs2CO3 3.85 g (9.8 mmol), followed by stirring at 90° C. for 12 hrs. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, diluted with ethylacetate, and washed with a saturated sodium bicarbonate solution and a saturated NaCl solution. After drying over magnesium sulfate and concentration in a vacuum, purification by column chromatography (developing solvent: ethylacetate/hexane=1/2) afforded 1.2 g of the title compound (yield 68%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with ethylacetate
  4. washwashed with a saturated sodium bicarbonate solution
  5. dry with materialAfter drying over magnesium sulfate and concentration in a vacuum, purification by column chromatography (developing solvent: ethylacetate/hexane=1/2)

Sources & evidence

ORD record
ord-6a6b579927554289a5a85726b9d31621
Source dataset
uspto-grants-2011_09
Patent number
US08026235B1

Reaction notes

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