Acetic Acid → HCID 86705127, compound

HRID 541553Notes

Reaction equation

HRID 541553 reaction equation
Cl[CH2:2][C:3]1[O:4][C:5](=[O:9])[O:6][C:7]=1[CH3:8].[Na+].[I-].O=C(C1C=CC=CC=1)C[O:15][C:16](=[O:44])[C@H:17]([OH:43])[CH2:18][N:19]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)=[CH:32][CH:31]=1)[NH:20][C:21]([C:23]1[O:27][N:26]=[C:25]([OH:28])[CH:24]=1)=[O:22].C(=O)([O-])[O-].[Cs+].[Cs+].CC(O)=O>CC(C)=O.[Zn]>[Cl:42][C:38]1[CH:37]=[C:36]([C:33]2[CH:32]=[CH:31][C:30]([CH2:29][N:19]([CH2:18][C@@H:17]([OH:43])[C:16]([OH:44])=[O:15])[NH:20][C:21]([C:23]3[O:27][N:26]=[C:25]([O:28][CH2:2][C:3]4[O:4][C:5](=[O:9])[O:6][C:7]=4[CH3:8])[CH:24]=3)=[O:22])=[CH:35][CH:34]=2)[CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 98555184-(Chloromethyl)-5-methyl-1,3-dioxol-2-oneHCID 178521475HCID 178521475, compound

Product 1

HCID 86705127HCID 86705127, compoundYield 14.1%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 180AcetoneSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 4-chloromethyl-5-methyl-1,3-dioxol-2-one (11.9 μL, 109 μmol) and NaI (16.4 mg, 109 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 (20.0 mg, 36.4 μmol) and cesium carbonate (14.2 mg, 43.6 μmol) in acetone (1 mL). The resulting mixture was stirred at 60° C. for 2 hours, concentrated, purified by flash chromatography (EtOAc/hexanes=0-100%). 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 solids were washed with AcOH (0.5 mL) then filtered. The filtrates were combined and purified by reverse phase preparative HPLC to yield the title compound (2.8 mg). MS m/z [M+H]+ calc'd for C25H22ClN3O9, 544.10. found 544.5.

Workup

  1. temperaturecooled to room temperature
  2. stirringThe resulting mixture was stirred at 60° C. for 2 hours
  3. concentrationconcentrated
  4. custompurified by flash chromatography (EtOAc/hexanes=0-100%)
  5. concentrationconcentrated
  6. stirringthe resulting mixture was stirred at room temperature for 2 hours
  7. washThe solids were washed with AcOH (0.5 mL)
  8. filtrationthen filtered
  9. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-bf8de49b1493472e95792638246de237
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

Loading…