Hydrochloric Acid → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid 2,2,2-Trifluoroethyl Ester

HRID 516446Notes

Reaction equation

HRID 516446 reaction equation
Cl.O1CCOCC1.C([O:10][C:11](=O)[C@H:12]([OH:42])[CH2:13][C@H:14]([NH:29][C:30]([C:32]1[CH:41]=[CH:40][C:35]2[N:36]=[N:37][N:38]([OH:39])[C:34]=2[CH:33]=1)=[O:31])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:18][CH:17]=1)C.[F:44][C:45]([F:49])([F:48])[CH2:46][OH:47]>>[F:44][C:45]([F:49])([F:48])[CH2:46][O:47][C:11](=[O:10])[C@H:12]([OH:42])[CH2:13][C@H:14]([NH:29][C:30]([C:32]1[CH:41]=[CH:40][C:35]2[N:36]=[N:37][N:38]([OH:39])[C:34]=2[CH:33]=1)=[O:31])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=2)=[CH:18][CH:17]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 64092,2,2-TrifluoroethanolHCID 312751,4-DioxaneHCID 67969574(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid Ethyl Ester

Product 1

HCID 72700396(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid 2,2,2-Trifluoroethyl EsterYield 27.5%

Conditions

Temperature
100 °C

Procedure

4.0 M HCl in 1,4-dioxane (196 μL, 786 μmol) was added to a solution of (2R,4R)-5-(3′-chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic acid ethyl ester (50.0 mg, 98.2 μmol) in 2,2,2-trifluoroethanol (215 μL, 3.0 mmol), and the resulting mixture was stirred at 100° C. for 3 hours. The mixture was concentrated in vacuo to yield a clear colorless liquid, which was purified by preparative HPLC (C18 column chromatography using 40-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (15.2 mg, purity 99%). MS m/z [M+H]+ calc'd for C26H22ClF3N4O5, 563.12. found 563.2.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto yield a clear colorless liquid, which
  3. customwas purified by preparative HPLC (C18 column chromatography using 40-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-5944fb46819c4bbc81ba8b4c9ac1b2eb
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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