Potassium Carbonate → (R)-3-[N'-t-Butoxycarbonyl-N-(3'-chlorobiphenyl-4-ylmethyl)-hydrazino]-2-hydroxy-propionic Acid

HRID 1043981Notes

Reaction equation

HRID 1043981 reaction equation
C[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:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[Cl:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O.[Cl-].[NH4+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:11]([O:10][C:8]([NH:7][N:6]([CH2:5][C@@H:4]([OH:23])[C:3]([OH:2])=[O:24])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:25])[CH:31]=2)=[CH:18][CH:17]=1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 67972599(R)-3-[N-(4-Bromobenzyl)-N'-t-butoxycarbonylhydrazino]-2-hydroxypropionic acid methyl ester

Product 1

HCID 67972781(R)-3-[N'-t-Butoxycarbonyl-N-(3'-chlorobiphenyl-4-ylmethyl)-hydrazino]-2-hydroxy-propionic Acid

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
90 °C

Procedure

(R)-3-[N-(4-Bromobenzyl)-N′-t-butoxycarbonyl-hydrazino]-2-hydroxy-propionic acid methyl ester (1.0 g, 2.5 mmol), 3-chlorophenylboronic acid (776 mg, 5.0 mmol), and K2CO3 (857 mg, 6.2 mmol) were dissolved in a mixture of THF (18 mL) and water (18 mL). The reaction flask was then purged with nitrogen and tetrakis(triphenylphosphine) palladium(0) (286 mg, 248 μmol) was added. The mixture was stirred at 90° C. overnight (˜18 hours). The mixture was diluted with saturated aqueous ammonium chloride and extracted with EtOAc. The organic layer was collected, dried and concentrated. The product was purified (Interchim reverse phase chromatography column, 10-80% MeCN in water) to yield the title compound.

Workup

  1. additionwas added
  2. extractionextracted with EtOAc
  3. customThe organic layer was collected
  4. customdried
  5. concentrationconcentrated
  6. customThe product was purified (Interchim reverse phase chromatography column, 10-80% MeCN in water)

Sources & evidence

ORD record
ord-69b9378ab8ac44f8b0ae67585f5fdf25
Source dataset
uspto-grants-2013_10
Patent number
US08563512B2

Reaction notes

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