Acetic Acid → HCID 117669084, compound

HRID 541550Notes

Reaction equation

HRID 541550 reaction equation
[C:1]([O:6][CH2:7]Cl)(=[O:5])[CH2:2][CH2:3][CH3:4].[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].CCN(CC)CC.CC(O)=O>CC(C)=O.[Zn]>[C:15]([C@H:16]([OH:42])[CH2:17][N:18]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[CH:36]=2)=[CH:33][CH:34]=1)[NH:19][C:20]([C:22]1[O:26][N:25]=[C:24]([O:27][CH2:7][O:6][C:1](=[O:5])[CH2:2][CH2:3][CH3:4])[CH:23]=1)=[O:21])([OH:43])=[O:14]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 8471TriethylamineHCID 2725008Chloromethyl butanoateHCID 178521475HCID 178521475, compound

Product 1

HCID 117669084HCID 117669084, compoundYield 8.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 180AcetoneSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of chloromethyl butyrate (20.5 μL, 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 Et3N (38.0 μL, 273 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 lyophilized. Zinc (178 mg, 2.7 mmol) and AcOH (1.0 mL, 18 mmol) was 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 (2.5 mg). MS m/z [M+H]+ calc'd for C25H26ClN3O8, 532.14. found 532.2.

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. stirringthe resulting mixture was stirred at room temperature for 2 hours
  8. filtrationThe mixture was filtered
  9. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-f0794b99defb45808dfe5c8a81f9ec0b
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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