Water → HCID 76578052, compound

HRID 910413Notes

Reaction equation

HRID 910413 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH:4]([NH:8][C:9](=[O:35])[CH:10]([NH:27][C:28]([O:30]C(C)(C)C)=O)[CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=2)=[CH:16][CH:15]=1)[CH:5]([CH3:7])[CH3:6].O.CCN(C(C)C)C(C)C.ClC(OC1C=CC=CC=1)=O>C(O)(C(F)(F)F)=O.O1CCOCC1.CN(C=O)C>[CH3:1][O:2][C:3](=[O:36])[CH:4]([N:8]1[C:9](=[O:35])[CH:10]([CH2:11][O:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[CH:18][CH:19]=2)[NH:27][C:28]1=[O:30])[CH:5]([CH3:6])[CH3:7]

Participants

8

Reactant 4

HCID 962WaterHCID 15891Phenyl chloroformateHCID 81531Diisopropylethylamine2×HCID 66661040HCID 66661040, compound

Product 1

HCID 76578052HCID 76578052, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

The compound obtained in step a above (20a) (813 mg, 1.619 mmol) was stirred in TFA (4 mL) at 0° C. for 5 h, then concentrated under vacuum. The residue was diluted with CH2Cl2, washed with saturated NaHCO3 and brine, dried over anhydrous Na2SO4 and concentrated which gave the crude product. The obtained crude product was stirred in dioxane (9 mL) and water (1 mL) at 0° C. DIEA (610 mg, 4.86 mmol) and phenyl chloroformate (379 mg, 2.429 mmol) were added, and the mixture was stirred for 2 h. The solvent was removed under vacuum; the residue was diluted with EtOAc and washed with brine. The combined organic layers were dried and concentrated to give a yellow oil. The obtained oil was then stirred with DIEA (610 mg, 4.86 mmol) in DMF (10 mL) for 24 h. After general workup, the crude product was purified by silica gel column chromatography which gave the title compound as a white solid (374 mg, 54% yield).

Workup

  1. concentrationconcentrated under vacuum
  2. additionThe residue was diluted with CH2Cl2
  3. washwashed with saturated NaHCO3 and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated which
  6. customgave the crude product
  7. customThe obtained crude product
  8. customat 0° C
  9. customThe solvent was removed under vacuum
  10. additionthe residue was diluted with EtOAc
  11. washwashed with brine
  12. customThe combined organic layers were dried
  13. concentrationconcentrated
  14. customto give a yellow oil
  15. customAfter general workup, the crude product was purified by silica gel column chromatography which

Sources & evidence

ORD record
ord-50a3b3d7411a4ff296ec896f5f671c7b
Source dataset
uspto-grants-2011_09
Patent number
US08022092B2

Reaction notes

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