Ethanol → (2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid

HRID 516467Notes

Reaction equation

HRID 516467 reaction equation
C([O:3][C:4](=[O:26])[C@H:5]([OH:25])[CH2:6][C@H:7]([NH:16][C:17]([C:19]1[N:20]=[N:21][N:22]([OH:24])[CH:23]=1)=[O:18])[CH2:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)C.[Cl:27][C:28]1[CH:29]=[CH:30][C:31]([F:37])=[C:32](B(O)O)[CH:33]=1.C([O-])([O-])=O.[K+].[K+].CCO.O.[Li+].[OH-]>[Pd]>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([F:37])=[C:30]([C:12]2[CH:11]=[CH:10][C:9]([CH2:8][C@@H:7]([NH:16][C:17]([C:19]3[N:20]=[N:21][N:22]([OH:24])[CH:23]=3)=[O:18])[CH2:6][C@@H:5]([OH:25])[C:4]([OH:3])=[O:26])=[CH:14][CH:13]=2)[CH:29]=1

Participants

8

Reactant 6

HCID 702EthanolHCID 962Water2×HCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 3718925(5-Chloro-2-fluoro-phenyl)boronic acidHCID 67969558(2R,4R)-5-(4-Bromophenyl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)amino]pentanoic Acid Ethyl Ester

Product 1

HCID 67969390(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic AcidYield 54.1%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

(2R,4R)-5-(4-Bromophenyl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)amino]pentanoic acid ethyl ester (30 mg, 70 μmol) was combined with 5-chloro-2-fluorophenylboronic acid (22 mg, 126 μmol), K2CO3 (29.1 mg, 211 μmol), EtOH (0.8 mL, 10 mmol), and water (0.2 mL, 10 mmol). SilicaCat DPP-Pd (0.28 mmol/g loading; 25.1 mg, 7.0 μmol) was added the last. The resulting mixture was microwaved at 100° C. for 10 minutes. 1 M LiOH in water (281 μL, 281 μmol) was added, and the resulting mixture was stirred for 1 hour. The mixture was filtered, concentrated, and purified by preparative HPLC to yield the title compound (17 mg). MS m/z [M+H]+ calc'd for C20H18ClFN4O5, 449.10. found 449.2.

Workup

  1. customThe resulting mixture was microwaved at 100° C. for 10 minutes
  2. filtrationThe mixture was filtered
  3. concentrationconcentrated
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-ee31aefa00874baf8be3a33f4da952c4
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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