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

HRID 516445Notes

Reaction equation

HRID 516445 reaction equation
Cl.O1CCOCC1.[CH2:8]([O:10][C:11](=[O:43])[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)[CH3:9].[F:44][C:45]([F:50])([F:49])CCO>>[F:44][C:45]([F:50])([F:49])[CH2:9][CH2:8][O:10][C:11](=[O:43])[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 312751,4-DioxaneHCID 1375123,3,3-Trifluoro-1-propanolHCID 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 72700394(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid 3,3,3-Trifluoropropyl EsterYield 31.8%

Conditions

Temperature
70 °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 3,3,3-trifluoropropan-1-ol (336 mg, 3.0 mmol), and the resulting mixture was stirred at 70° C. for 3 hours. The mixture was concentrated in vacuo to yield a white solid, 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 (18 mg, purity 100%). MS m/z [M+H]+ calc'd for C27H24ClF3N4O5, 577.14. found 577.1.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto yield a white solid, 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-b7ddcce178a34ff9b2887dff3ced2a47
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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