Sodium Carbonate → HCID 58765697, compound

HRID 860696Notes

Reaction equation

HRID 860696 reaction equation
[CH3:1][O:2][C:3](=[O:38])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]([C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25](B4OC(C)(C)C(C)(C)O4)=[CH:24][CH:23]=3)[S:19][C:20]=2[CH3:21])[CH3:15])=[CH:8][C:7]=1[CH3:37].Br[C:40]1[N:45]=[CH:44][CH:43]=[CH:42][N:41]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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]>[CH3:1][O:2][C:3](=[O:38])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH:14]([C:16]2[N:17]=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([C:40]4[N:45]=[CH:44][CH:43]=[CH:42][N:41]=4)=[CH:24][CH:23]=3)[S:19][C:20]=2[CH3:21])[CH3:15])=[CH:8][C:7]=1[CH3:37]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 783452-BromopyrimidineHCID 58765844HCID 58765844, compound

Product 1

HCID 58765697HCID 58765697, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

3-[2-Methyl-4-(2-(5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-thiazol-4-yl)-propoxy)-phenyl]-propionic acid methyl ester (5.2 g, 6.92 mmol) is dissolved in anhydrous toluene (30 mL), degassed, and filled with nitrogen three times. [1,1′-Bis-(diphenylphosphino)ferrocene]dichloropalladium(II) (330 mg, 0.346 mmol), 2-bromopyrimidine (2.24 g, 14 mmol), and sodium carbonate (3.71 g in 5 mL water, 35 mmol) are added, and the degassing procedure is repeated. The reaction is heated to 100° C. and monitored by HPLC. Upon complete consumption of starting material, the reaction is allowed to cool to room temperature and diluted with ethyl acetate. Celite is added and the mixture is filtered and rinsed with more ethyl acetate and water. The solution is further diluted with water and the two phases are separated. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The pure 3-(2-Methyl-4-{2-[5-methyl-2-(4-pyrimidin-2-yl-phenyl)-thiazol-4-yl]-propoxy}-phenyl)-propionic acid methyl ester (1.3 g, 2.87 mmol) is obtained after column chromatography (65% yield).

Workup

  1. customdegassed
  2. additionfilled with nitrogen three times
  3. customUpon complete consumption of starting material
  4. temperatureto cool to room temperature
  5. additiondiluted with ethyl acetate
  6. additionCelite is added
  7. filtrationthe mixture is filtered
  8. washrinsed with more ethyl acetate and water
  9. additionThe solution is further diluted with water
  10. customthe two phases are separated
  11. washThe organic layer is washed with water and brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-9c0473b7a38042fe974fdf3520b9f3fa
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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