Potassium Carbonate → HCID 67972667, compound

HRID 2363257Notes

Reaction equation

HRID 2363257 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C@H:4]([OH:23])[CH2:5][N:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1)[NH:7]C(OC(C)(C)C)=O.[Cl:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.[C:35]([O-])([O-])=O.[K+].[K+]>CCO.O>[CH2:1]([O:2][C:3](=[O:24])[C@H:4]([OH:23])[CH2:5][N:6]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:25])[CH:31]=2)=[CH:20][CH:21]=1)[NH2:7])[CH3:35]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 67972599HCID 67972599, compound

Product 1

HCID 67972667HCID 67972667, compoundYield 71.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

(R)-3-[N-(4-Bromobenzyl)-N′-t-butoxycarbonylhydrazino]-2-hydroxypropionic acid methyl ester (600 mg, 1 mmol), 3-chlorophenylboronic acid (419 mg, 2.7 mmol), and K2CO3 (617 mg, 4.5 mmol) were combined in EtOH (5 mL) and water (1 mL), followed by the addition of SilicaCat®Pd(0) (0.09 mmol/g loading, 1160 mg, 104 μmol). The mixture was heated in a microwave reactor at 120° C. until the reaction was complete (˜30 minutes). The mixture was filtered and concentrated. The residue was dissolved into MeCN/AcOH and purified by reverse phase chromatography (55 g column; gradient 30-95% MeCN in water with 0.1% TFA). The clean fractions were collected, concentrated and then dissolved in 4M HCl in dioxane (6 mL) and EtOH (6 mL). The mixture was stirred at room temperature overnight, then concentrated to yield the title compound (250 mg), which was used without further purification.

Workup

  1. custom(˜30 minutes)
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved into MeCN/AcOH
  5. custompurified by reverse phase chromatography (55 g column; gradient 30-95% MeCN in water with 0.1% TFA)
  6. customThe clean fractions were collected
  7. concentrationconcentrated
  8. dissolutiondissolved in 4M HCl in dioxane (6 mL)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-26577b48747a4105a77d650a5ca3d464
Source dataset
uspto-grants-2014_04
Patent number
US08691868B2

Reaction notes

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