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

HRID 516452Notes

Reaction equation

HRID 516452 reaction equation
Cl.O1CCOCC1.[Cl:8][C:9]1[CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C@@H:22]([NH:29][C:30]([C:32]3[CH:41]=[CH:40][C:35]4[N:36]=[N:37][N:38]([OH:39])[C:34]=4[CH:33]=3)=[O:31])[CH2:23][C@@H:24]([OH:28])[C:25]([OH:27])=[O:26])=[CH:17][CH:16]=2)[CH:12]=[CH:13][CH:14]=1.[CH2:42](O)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>>[CH2:42]([O:26][C:25](=[O:27])[C@H:24]([OH:28])[CH2:23][C@H:22]([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])[CH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[CH:10]=2)=[CH:20][CH:19]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

5

Reactant 4

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 67970017(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid

Product 1

HCID 72700648(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid Benzyl EsterYield 10.4%

Conditions

Temperature
60 °C

Procedure

4.0 M HCl in 1,4-dioxane (270 μL, 1.0 mmol) 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 (130 mg, 270 μmol) in benzyl alcohol (559 μL, 5.4 mmol), and the resulting mixture was stirred at 60° C. for 15 minutes. The mixture was purified by preparative HPLC (C18 column chromatography using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as an off-white solid (16.0 mg, purity 99.2%). MS m/z [M+H]+ calc'd for C31H27ClN4O5, 571.17. found 571.1.

Workup

  1. customThe mixture was purified by preparative HPLC (C18 column chromatography using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-b73f0b76aa2340999fb3bfedbe75949d
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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