Acetic Acid → (R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid Acetoxymethyl Ester

HRID 541519Notes

Reaction equation

HRID 541519 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:32])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH2:26][C@@H:27]([OH:31])[C:28]([OH:30])=[O:29])[NH:16][C:17]([C:19]3[O:23][N:22]=[C:21]([O:24][CH3:25])[CH:20]=3)=[O:18])=[CH:10][CH:9]=2)[CH:7]=1.CC(C)=O.[C:37]([O:40][CH2:41]Br)(=[O:39])[CH3:38].CCN(CC)CC.CC(O)=O>>[C:37]([O:40][CH2:41][O:29][C:28](=[O:30])[C@H:27]([OH:31])[CH2:26][N:15]([CH2:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[F:32])=[CH:13][CH:12]=1)[NH:16][C:17]([C:19]1[O:23][N:22]=[C:21]([O:24][CH3:25])[CH:20]=1)=[O:18])(=[O:39])[CH3:38]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 180AcetoneHCID 8471TriethylamineHCID 68536Bromomethyl acetateHCID 67972936(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid

Product 1

HCID 86705097(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid Acetoxymethyl EsterYield 26.7%

Procedure

To a solution of (R)-3-[N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid (40.0 mg, 0.1 mmol) in acetone (1.0 mL, 14 mmol) was added bromomethyl acetate (16.9 μL, 172 μmol) followed by Et3N (24.0 μL, 172 μmol), and resulting mixture was stirred for 90 minutes. The reaction was quenched with AcOH (19.6 μL, 345 μmol) and the mixture was concentrated. The residue was dissolved in AcOH (3 mL), filtered, and purified by reverse phase preparative HPLC. The desired fractions were combined and lyophilized. The solid was dissolved in AcOH (1.5 mL), filtered, and purified by reverse phase preparative HPLC to yield the title compound (14.3 mg, purity 97.8%) as a TFA salt. MS m/z [M+H]+ calc'd for C24H23ClFN3O8, 536.12. found 536.2.

Workup

  1. customresulting mixture
  2. concentrationthe mixture was concentrated
  3. dissolutionThe residue was dissolved in AcOH (3 mL)
  4. filtrationfiltered
  5. custompurified by reverse phase preparative HPLC
  6. dissolutionThe solid was dissolved in AcOH (1.5 mL)
  7. filtrationfiltered
  8. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-06789b2b9c044b07b0fff5758458ddcf
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

Loading…