Diethyl Oxalate → HCID 11190201, compound

HRID 351634Notes

Reaction equation

HRID 351634 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([NH:20][C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:32](OCC)(=[O:38])[C:33]([O:35][CH2:36][CH3:37])=[O:34].[Cl-].[NH4+]>O1CCCC1>[CH2:36]([O:35][C:33](=[O:34])[C:32]([C:15]1[C:16]([NH:20][C:21](=[O:26])[C:22]([CH3:23])([CH3:25])[CH3:24])=[CH:17][CH:18]=[CH:19][C:14]=1[N:11]1[CH2:10][CH2:9][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:13][CH2:12]1)=[O:38])[CH3:37]

Participants

6

Reactant 4

HCID 7268Diethyl OxalateHCID 25517Ammonium ChlorideHCID 22714253HCID 22714253, compoundHCID 178418339Butyllithium

Product 1

HCID 11190201HCID 11190201, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
15 °C

Procedure

Under a nitrogen atmosphere, a solution of N-[3-(4-benzyl-piperazin-1-yl)-phenyl]-2,2-dimethyl-propionamide (2.4 g, 6.8 mmol) and N,N,N′N′-tetramethylethylenediamine (3.2 g, 27.4 mmol) in tetrahydrofuran (24 mL) was stirred for 15 minutes at 0° C., n-butyllithium (2.5M in hexane) (11 mL, 27.5 mmol) was added dropwise, and the mixture stirred for 3 hours at 15° C. The mixture was then cooled to −78° C., and diethyl oxalate (4.0 g, 27.4 mmol) was added. The mixture was stirred at −20° C. for 30 minutes, poured into a saturated aqueous solution of ammonium chloride (50 mL), and the product extracted into ethyl acetate (3×30 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and the solvent removed under vacuum to yield 4.5 g of crude product as a light brown oil. Purification by chromatography (150 g silica gel, 2% methanol in chloroform) afforded the title compound (1.5 g, 3.3 mmol, 49% yield) as a straw colored oil; this compound was confirmed by the following mass spectrometry results: EI M+ @ m/z 451 and (+)FAB [M+H]+ @ m/z 452, [M+Na]+ @ m/z 474.

Workup

  1. temperatureThe mixture was then cooled to −78° C.
  2. stirringThe mixture was stirred at −20° C. for 30 minutes
  3. extractionthe product extracted into ethyl acetate (3×30 mL)
  4. washThe combined organic layers were washed with brine (20 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under vacuum
  8. customto yield 4.5 g of crude product as a light brown oil
  9. customPurification by chromatography (150 g silica gel, 2% methanol in chloroform)

Sources & evidence

ORD record
ord-436dc158e90b463095d513c6dbad6249
Source dataset
uspto-grants-2004_06
Patent number
US06743796B2

Reaction notes

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