Tetrahydrofuran → HCID 57860161, compound

HRID 1947135Notes

Reaction equation

HRID 1947135 reaction equation
Cl.[CH2:2]([C:4]1[N:9]([CH2:10][C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8](=[O:19])[C:7]2[C:20]([O:33][CH3:34])=[C:21]([C:24]([NH:26][CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:25])[N:22]([CH3:23])[C:6]=2[CH:5]=1)[CH3:3].C(N(CC)CC)C.C1COCC1.C([O:50][CH2:51][C:52](Cl)=[O:53])(=O)C>C(OCC)(=O)C>[CH2:2]([C:4]1[N:9]([CH2:10][C:11](=[O:18])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:8](=[O:19])[C:7]2[C:20]([O:33][CH3:34])=[C:21]([C:24]([NH:26][CH:27]3[CH2:28][CH2:29][N:30]([C:51](=[O:50])[CH2:52][OH:53])[CH2:31][CH2:32]3)=[O:25])[N:22]([CH3:23])[C:6]=2[CH:5]=1)[CH3:3]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 66892222HCID 66892222, compound

Product 1

HCID 57860161HCID 57860161, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of the compound of Example 130 (90.0 mg, 0.185 mmol), triethylamine (76.9 μL, 0.555 mmol) and THF (5 mL) was added acetoxyacetyl chloride (23.8 μL, 0.221 mmol) at 0° C., and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by aminosilica gel chromatography (eluate; ethyl acetate), and the obtained solid was dissolved in THF (1.2 mL)-ethanol (2.5 mL). 8N Aqueous sodium hydroxide solution (250 μL) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with water, acidified with 6N hydrochloric acid (0.5 mL), and extracted twice with ethyl acetate. The extract was combined, washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by aminosilica gel chromatography (eluate; ethyl acetate/methanol=10/0-9/1), and the obtained solid was recrystallized from ethyl acetate to give the title compound (61.2 mg, 65%) as white crystals.

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by aminosilica gel chromatography (eluate; ethyl acetate)
  5. dissolutionthe obtained solid was dissolved in THF (1.2 mL)-ethanol (2.5 mL)
  6. addition8N Aqueous sodium hydroxide solution (250 μL) was added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was diluted with water
  9. extractionextracted twice with ethyl acetate
  10. washwashed with saturated brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by aminosilica gel chromatography (eluate; ethyl acetate/methanol=10/0-9/1)
  14. customthe obtained solid was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-39f730a3da184bcdb492b2b11c63bde2
Source dataset
uspto-grants-2013_03
Patent number
US08399449B2

Reaction notes

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