Sodium Carbonate → (4-[6-Amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy)acetic acid ethyl ester

HRID 425931Notes

Reaction equation

HRID 425931 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:18])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH2:19]([O:21][C:22](=[O:40])[CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28](C2OC(C)(C)C(C)(C)O2)=[CH:27][CH:26]=1)[CH3:20].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.CN(C=O)C.O.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:19]([O:21][C:22](=[O:40])[CH2:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[CH:7]=[N:6][C:5]([NH2:8])=[C:4]([O:9][CH2:10][C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[CH:3]=2)=[CH:27][CH:26]=1)[CH3:20]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 211114873-(2,6-Dichlorobenzyloxy)-5-bromopyridin-2-amineHCID 66701800[4-(4,4,5,5-Tetramethyl-(1,3]dioxolan-2-yl)-phenoxy]-acetic acid ethyl ester

Product 1

HCID 66701842(4-[6-Amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy)acetic acid ethyl ester

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 5-bromo-3-(2,6-dichloro-benzyloxy)-pyridin-2-ylamine (Example I(a)) (2.2 g, 6.3 mmol), [4-(4,4,5,5-tetramethyl-[1,3]dioxolan-2-yl)-phenoxy]-acetic acid ethyl ester (2.9 g, 1.5 eq.), bis(triphenylphosphine)palladium(II) chloride (136 mg) and sodium carbonate (1.93 g, 3.0 eq.) in ethylene glycol dimethyl ether (30 mL), DMF (5 mL) and water (8 mL) was heated to 90-100° C. under nitrogen for 7 hr. The reaction was cooled to rt and diluted with ethyl acetate. The mixture was washed with water, brine, dried and purified on silica column to afford {4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy}-acetic acid ethyl ester. This ester was treated with sodium carbonate and water at rt overnight. The reaction was diluted with ethyl acetate. The mixture was washed with water, brine, dried and purified on silica column to afford 4-[6-amino-5-(2,6-dichloro-benzyloxy)-pyridin-3-yl]-phenoxy}-acetic acid.

Workup

  1. temperatureThe reaction was cooled to rt
  2. washThe mixture was washed with water, brine
  3. customdried
  4. custompurified on silica column

Sources & evidence

ORD record
ord-28d1f0ddea9d47568046e530eb6aadd6
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

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