Water → Ethyl 3-(5-(4,5-difluoro-2-(hydroxymethyl)phenyl)picolinamido)propanoate

HRID 405206Notes

Reaction equation

HRID 405206 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[CH2:10][OH:11].CC1(C)C(C)(C)OB([C:20]2[CH:21]=[CH:22][C:23]([C:26]([NH:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:27])=[N:24][CH:25]=2)O1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:9][C:5]1[C:6]([F:8])=[CH:7][C:2]([C:20]2[CH:21]=[CH:22][C:23]([C:26]([NH:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[O:27])=[N:24][CH:25]=2)=[C:3]([CH2:10][OH:11])[CH:4]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57518297(2-Bromo-4,5-difluorophenyl)methanolHCID 71059832Ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoate

Product 1

HCID 71060054Ethyl 3-(5-(4,5-difluoro-2-(hydroxymethyl)phenyl)picolinamido)propanoate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

(2-bromo-4,5-difluorophenyl)methanol (2.8 g, 12.5 mmol), ethyl 3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamido)propanoate (4.8 g, 13.7 mmol), Pd(dppf)Cl2 (1.4 g, 1.9 mmol), and K2CO3 (3.4 g, 24.9 mmol) were dissolved in 1,4-dioxane (28 mL) and water (15 mL) and the resulting mixture was heated to 85° C. After 2 h the resulting mixture was diluted with EtOAc and the layers were separated. The organic layer was dried (Na2SO4), concentrated, and purified via column chromatography to yield the title compound.

Workup

  1. customthe layers were separated
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated
  4. custompurified via column chromatography

Sources & evidence

ORD record
ord-5e370d896edc455ab4047138d7c959f9
Source dataset
uspto-grants-2014_06
Patent number
US08748624B2

Reaction notes

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