Potassium Phosphate, Tribasic → 2-(4-(Pyrazin-2-yl)phenyl)acetic acid

HRID 474141

Reaction equation

HRID 474141 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:10]=2)O1.I[C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[N:22]1[CH:23]=[CH:24][N:25]=[CH:26][C:21]=1[C:9]1[CH:10]=[CH:11][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:13][CH:14]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 642841IodopyrazineHCID 37190022-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic Acid

Product 1

HCID 595359382-(4-(Pyrazin-2-yl)phenyl)acetic acidYield 32%

Reagents, catalysts & solvents 3

HCID 75806TricyclohexylphosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 0.40 g (1.53 mmol) of [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetic acid in 4.0 ml of dioxane was added 0.18 mL (1.73 mmol) of 2-iodopyrazine, 10.3 mg (0.037 mmol) of tricyclohexylphosphine, 13.9 mg (0.015 mmol) of Pd2(dba)3, and 2.0 ml (1.27 M, 2.59 mmol) of aqueous potassium phosphate solution. The resulting suspension was degassed for 10 mins. After 30 min in the microwave at 150° C., the reaction mixture was cooled, acidified with 1N HCl, extracted with ethyl acetate, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18) afforded 0.10 g (32%) of (4-pyrazin-2-ylphenyl)acetic acid. 1H NMR (CD3OD, 400 MHz) 9.1 (s, 1H); 8.66 (t, J=1.74 Hz, 1H); 8.51 (d, J=2.57 Hz, 1H); 8.04 (d, J=8.15 Hz, 2H); 7.46 (d, J=8.15 Hz, 2H); 3.70 (s, 2H). ES-MS M+1=215.1.

Workup

  1. customThe resulting suspension was degassed for 10 mins
  2. temperaturethe reaction mixture was cooled
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification
  9. additionby preparative HPLC (5->95% CH3CN/H2O over 15 min, 0.05% added TFA, C18)

Sources & evidence

ORD record
ord-cec6615b53614e45a6d4766dc3e42e06
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Linked notes

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