Acetone → (2R,4R)-4-[(3-Acetoxymethoxy-3H-benzotriazole-5-carbonyl)amino]-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic Acid Acetoxymethyl Ester

HRID 516451Notes

Reaction equation

HRID 516451 reaction equation
[CH3:1]CN(CC)CC.[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.[C:42]([O:45][CH2:46]Br)(=[O:44])[CH3:43].CC(C)=O.[C:52]([OH:58])([C:54](F)(F)F)=[O:53].C(Cl)Cl>>[C:42]([O:45][CH2:46][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]([O:39][CH2:1][O:58][C:52](=[O:53])[CH3:54])[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)(=[O:44])[CH3:43]

Participants

6

Reactant 5

HCID 180AcetoneHCID 8471TriethylamineHCID 68536Bromomethyl acetateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 67970017(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid

Product 1

HCID 72700646(2R,4R)-4-[(3-Acetoxymethoxy-3H-benzotriazole-5-carbonyl)amino]-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic Acid Acetoxymethyl EsterYield 19.8%

Conditions

Temperature
65 °C

Procedure

Et3N (7.0 μL, 50 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 (20.0 mg, 42 μmol) and bromomethyl acetate (6.52 μL, 67 μmol) in acetone (1.3 mL, 17.2 mmol), and the resulting mixture was stirred in a sealed vial at 65° C. for 5 hours. 1:1 TFA/DCM (0.50 mL, 3.1 mmol) was added, and the mixture was stirred at room temperature for 30 minutes and concentrated to yield a clear yellow liquid. The crude liquid was purified by preparative HPLC (C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound (5.2 mg, purity 100%). MS m/z [M+H]+ calc'd for C30H29ClN4O9, 625.16. found 625.1.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. concentrationconcentrated
  3. customto yield a clear yellow liquid
  4. customThe crude liquid was purified by preparative HPLC (C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-c6a4cbe75eab4c8684ff7f57f342dfa2
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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