Hydrochloric Acid → HCID 54679849, compound

HRID 2109865Notes

Reaction equation

HRID 2109865 reaction equation
[C:1]([N:4]1[CH:10]2[CH:8]([CH:9]2[CH2:11][O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:7]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[C:6](=[O:28])[CH2:5]1)(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[C:44](OCC)(=[O:50])[C:45](OCC)=[O:46].Cl>CN(C=O)C>[CH2:13]([O:12][CH2:11][CH:9]1[CH:10]2[CH:8]1[N:7]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[C:6](=[O:28])[C:5]1[N:4]2[C:1](=[O:3])[CH:2]=[C:44]([OH:50])[C:45]=1[OH:46])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 8028TetrahydrofuranHCID 2733832Lithium Hexamethyldisilazide2×HCID 68832696HCID 68832696, compound

Product 1

HCID 54679849HCID 54679849, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a cold (0° C.) solution of 5-acetyl-2-(4-fluorobenzyl)-7-[(benzyloxy)-methyl]-2,5-diazabicyclo[4.1.0]heptane-3-one (700 mg, 1.83 mmol) in DMF (10 mL) under nitrogen, a solution of lithium bis(trimethylsilyl)amide in THF (1.0 M, 2.0 mL, 2.0 mmol) was added. After 30 min, diethyl oxalate (401 mg, 2.74 mmol) in DMF (2 mL) was added. After stirring for 1 h at room temperature, the resultant mixture was treated with additional lithium bis(trimethylsilyl)amide (1.0 M, 7.1 mL, 7.1 mmol), and stirred at room temperature overnight. The reaction mixture was treated with 1 N HCl, concentrated under vacuum. The residue was partitioned between brine and chloroform. The aqueous layer was extracted with chloroform twice. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was subjected to HPLC purification on C-18 stationary phase eluted with water/acetonitrile/TFA mobile phase. Collection and lyophilization of appropriate fractions provided the title compound.

Workup

  1. stirringstirred at room temperature overnight
  2. concentrationconcentrated under vacuum
  3. customThe residue was partitioned between brine and chloroform
  4. extractionThe aqueous layer was extracted with chloroform twice
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was subjected to HPLC purification on C-18 stationary phase
  9. washeluted with water/acetonitrile/TFA mobile phase
  10. customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record
ord-b91c8efbb75a4f3aa69dfb645b4fb5fb
Source dataset
uspto-grants-2009_04
Patent number
US07517532B2

Reaction notes

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