Diethyl Oxalate → HCID 54705274, compound

HRID 2109849Notes

Reaction equation

HRID 2109849 reaction equation
[C:1]([N:4]1[CH:9]([CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][S:12]2(=[O:18])=[O:17])[CH2:8][N:7]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[C:6](=[O:27])[CH2:5]1)(=[O:3])[CH3:2].[C:28](OCC)(=[O:34])[C:29](OCC)=[O:30].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>CN(C=O)C>[O:17]=[S:12]1(=[O:18])[CH2:13][CH2:14][CH2:15][CH2:16][N:11]1[CH2:10][CH:9]1[N:4]2[C:1](=[O:3])[CH:2]=[C:28]([OH:34])[C:29]([OH:30])=[C:5]2[C:6](=[O:27])[N:7]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[CH2:8]1

Participants

6

Reactant 4

HCID 7268Diethyl OxalateHCID 8028Tetrahydrofuran2×HCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 576346514-Acetyl-5-[(1,1-Dioxido-1,2-thiazinan-2-yl)methyl]-1-(4-fluorobenzyl)-piperazin-2-one

Product 1

HCID 54705274HCID 54705274, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold (0° C.) solution of 4-acetyl-5-[(1,1-dioxido-1,2-thiazinan-2-yl)methyl]-1-(4-fluorobenzyl)-piperazin-2-one (75 mg, 0.19 mmol) and diethyl oxalate (29 μL, 0.21 mmol) in DMF (3 mL) under an atmosphere of nitrogen, a solution of sodium bis(trimethylsilyl)amide in THF (1M, 0.21 mL, 0.21 mmol) was added over a period of 0.5 h and stirred at the temperature for 30 min. Then additional sodium bis(trimethylsilyl)amide in THF (1M, 0.21 mL, 0.21 mmol) was added over a period of 0.5 h and stirred at the temperature for 1 h. The product mixture was concentrated under vacuum, and the residue partitioned between aqueous HCl and ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. 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 the temperature for 1 h
  2. concentrationThe product mixture was concentrated under vacuum
  3. customthe residue partitioned between aqueous HCl and ethyl acetate
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  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-fb74c6886a72467d887c50102143032b
Source dataset
uspto-grants-2009_04
Patent number
US07517532B2

Reaction notes

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