Acetic Acid → HCID 86705124, compound

HRID 541551Notes

Reaction equation

HRID 541551 reaction equation
[C:1](=[O:8])([O:5][CH2:6][CH3:7])[O:2][CH2:3]Cl.[Na+].[I-].O=C(C1C=CC=CC=1)C[O:14][C:15](=[O:43])[C@H:16]([OH:42])[CH2:17][N:18]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=2)=[CH:31][CH:30]=1)[NH:19][C:20]([C:22]1[O:26][N:25]=[C:24]([OH:27])[CH:23]=1)=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].CC(O)=O>CC(C)=O.[Zn]>[Cl:41][C:37]1[CH:36]=[C:35]([C:32]2[CH:31]=[CH:30][C:29]([CH2:28][N:18]([CH2:17][C@@H:16]([OH:42])[C:15]([OH:43])=[O:14])[NH:19][C:20]([C:22]3[O:26][N:25]=[C:24]([O:27][CH2:3][O:2][C:1]([O:5][CH2:6][CH3:7])=[O:8])[CH:23]=3)=[O:21])=[CH:34][CH:33]=2)[CH:40]=[CH:39][CH:38]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 5325479Chloromethyl Ethyl CarbonateHCID 178521475HCID 178521475, compound

Product 1

HCID 86705124HCID 86705124, compoundYield 7.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 180AcetoneSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of chloromethyl ethyl carbonate (22.7 mg, 164 μmol) and NaI (24.5 mg, 164 μmol) in acetone (2.0 mL, 27 mmol) was stirred at 60° C. for 1 hour, then cooled to room temperature and added to a mixture of (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′-(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid 2-oxo-2-phenylethyl ester (30.0 mg, 54.5 μmol) and cesium carbonate (17.8 mg, 0.054.5 μmol) in acetone (1 mL). The resulting mixture was stirred at room temperature for 2 hours, concentrated, dissolved in AcOH (2 mL), filtered, and purified by reverse phase preparative HPLC. The desired fractions were combined and concentrated. Zinc (178 mg, 2.7 mmol) and AcOH (1.0 mL, 18 mmol) were added and the resulting mixture was stirred at room temperature for 2 hours. The mixture was filtered and purified by reverse phase preparative HPLC to yield the title compound (2.2 mg). MS m/z [M+H]+ calc'd for C24H24ClN3O9, 534.12. found 534.3.

Workup

  1. temperaturecooled to room temperature
  2. stirringThe resulting mixture was stirred at room temperature for 2 hours
  3. concentrationconcentrated
  4. dissolutiondissolved in AcOH (2 mL)
  5. filtrationfiltered
  6. custompurified by reverse phase preparative HPLC
  7. concentrationconcentrated
  8. stirringthe resulting mixture was stirred at room temperature for 2 hours
  9. filtrationThe mixture was filtered
  10. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-b805ed5bc36f44faba74f255e66a46f6
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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