Acetone → (2R,4R)-4-[(1-Butyryloxymethoxy-1H-[1,2,3]triazole-4-carbonyl)amino]-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxypentanoic Acid

HRID 516471Notes

Reaction equation

HRID 516471 reaction equation
[C:1]([O:6][CH2:7]Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([F:39])=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][C@@H:23]([NH:30][C:31]([C:33]3[N:34]=[N:35][N:36]([OH:38])[CH:37]=3)=[O:32])[CH2:24][C@@H:25]([OH:29])[C:26]([OH:28])=[O:27])=[CH:18][CH:17]=2)[CH:15]=1.CC(C)=O.CCN(CC)CC>>[C:1]([O:6][CH2:7][O:38][N:36]1[CH:37]=[C:33]([C:31]([NH:30][C@H:23]([CH2:22][C:19]2[CH:20]=[CH:21][C:16]([C:14]3[CH:15]=[C:10]([Cl:9])[CH:11]=[CH:12][C:13]=3[F:39])=[CH:17][CH:18]=2)[CH2:24][C@@H:25]([OH:29])[C:26]([OH:28])=[O:27])=[O:32])[N:34]=[N:35]1)(=[O:5])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 4

HCID 180AcetoneHCID 8471TriethylamineHCID 2725008Chloromethyl butanoateHCID 67969390(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid

Product 1

HCID 86705159(2R,4R)-4-[(1-Butyryloxymethoxy-1H-[1,2,3]triazole-4-carbonyl)amino]-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxypentanoic AcidYield 16.4%

Conditions

Temperature
65 °C

Procedure

Chloromethyl butyrate (13.7 mg, 100 μmol) was added to a solution of (2R,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)amino]pentanoic acid (30.0 mg, 66.8 μmol) in acetone (0.5 mL, 6.8 mmol). Et3N (18.6 μL, 134 μmol) was added and the resulting mixture was stirred at 65° C. for 2 hours. The mixture was then concentrated in vacuo to yield a yellow liquid. The crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (6.0 mg). MS m/z [M+H]+ calc'd for C25H26ClFN4O7, 549.15. found 549.1.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customto yield a yellow liquid
  3. customThe crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-028a2fca226e4dd79d571027a3a5fdef
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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