Potassium Phosphate, Tribasic → Methyl [4-(3-cyclopropylpyrazin-2-yl)phenyl]acetate

HRID 474144

Reaction equation

HRID 474144 reaction equation
Cl[C:2]1[C:3]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:9]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.O.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]>[CH:19]1([C:2]2[C:3]([C:8]3[CH:13]=[CH:12][C:11]([CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:9]=3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:21][CH2:20]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 59535943Methyl 2-(4-(3-chloropyrazin-2-yl)phenyl)acetate

Product 1

HCID 59535940Methyl [4-(3-cyclopropylpyrazin-2-yl)phenyl]acetateYield 65.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 0.15 g (0.57 mmol) of methyl [4-(3-chloropyrazin-2-yl)phenyl]acetate acid in 3.0 mL of toluene and 0.15 mL of water were added 63.8 mg (0.74 mmol) of cyclopropyl boronic acid, 16 mg (0.06 mmol) of tricyclohexylphosphine, 7.8 mg (0.009 mmol) of Pd2(dba)3, and 0.42 g (2.0 mmol) of potassium phosphate. The resulting suspension was degassed for 10 minutes. After 1 h in the microwave at 140° C., the reaction mixture was cooled, diluted with CH2Cl2, wash three times with water, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 0-40% EtOAc in hexanes) afforded 0.10 g (65%) methyl [4-(3-cyclopropylpyrazin-2-yl)phenyl]acetate. 1H NMR (CDCl3, 400 MHz) δ 8.35 (m, 2H); 7.68 (d, J=8.06 Hz, 2H); 7.41 (d, J=8.06 Hz, 2H); 3.72 (s, 3H); 3.71 (s, 2H); 2.22 (m, 1H); 1.19 (m, 2H); 0.99 (m, 2H). ES-MS M+1=269.1.

Workup

  1. customThe resulting suspension was degassed for 10 minutes
  2. temperaturethe reaction mixture was cooled
  3. additiondiluted with CH2Cl2
  4. washwash three times with water
  5. washwashed with brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (silica gel, linear gradient 0-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6249aada39304de5ad02af7adb819570
Source dataset
uspto-grants-2014_01
Patent number
US08637513B2

Linked notes

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