Diethyl Oxalate → HCID 135848644, compound

HRID 1372201Notes

Reaction equation

HRID 1372201 reaction equation
[C:1]([O:8][CH2:9][CH3:10])(=[O:7])[C:2](OCC)=O.[CH2:11]([O:18][CH2:19][C:20]([O:22]CC)=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[H-].[Na+].Cl.[CH3:28][S:29][CH2:30][CH2:31][O:32][CH2:33][C:34]([NH2:36])=[NH:35].[O-]CC.[Na+]>O1CCCC1.C(O)(=O)C.C(O)C>[CH2:11]([O:18][C:19]1[C:20](=[O:22])[NH:36][C:34]([CH2:33][O:32][CH2:31][CH2:30][S:29][CH3:28])=[N:35][C:2]=1[C:1]([O:8][CH2:9][CH3:10])=[O:7])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

9

Reactant 5

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 290299Ethyl 2-(benzyloxy)acetateHCID 2723922Sodium ethoxideHCID 21069788HCID 21069788, compound

Product 1

HCID 135848644HCID 135848644, compoundYield 10.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

Diethyl oxalate (2.77 g, 19.0 mmol) and ethyl benzyloxyacetate (3.69 g, 19.0 mmol) in dry tetrahydrofuran (30 ml) were treated at 22° C. with sodium hydride (0.83 g of a 60% dispersion in mineral oil, 20.9 mmol) followed by ethanol (10 μl) and the resulting mixture was stirred at 22° C. for 18 h. The tetrahydrofuran was evaporated under reduced pressure to give an orange syrup. A mixture of intermediate 3, 2-(2-(methylthio)ethoxy)acetamidine hydrochloride salt, (3.50 g, 19.0 mmol) in a solution of sodium ethoxide (9.5 mmol, prepared from 0.22 g of sodium in ethanol 25 ml) was then added all at once to the above adduct and the resulting mixture heated at 60° C. for 3 h. Acetic acid (2 ml) was added and the ethanol was evaporated under reduced pressure. The residue was diluted with ethyl acetate washed successively with saturated sodium bicarbonate and brine, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography on silica gel (elution with a gradient of ethyl acetate 20–30% in toluene) gave 0.728 g (10% yield) of the title ester as a clear oil. 1HNMR 400 MHz (CDCl3) δ (ppm): 1.33 (3H, t, J=7.1 Hz, CH3), 2.18 (3H, s, SCH3), 2.78 (2H, t, J=6.0 Hz, CH2), 3.78 (2H, t, J=6.0 Hz, CH2), 4.36 (2H, q, J=7.1 Hz, OCH2), 4.54 (2H, s, OCH2), 5.35 (2H, s, OCH2), 7.37 (3H, m, aromatics), 7.48 (2H, m, aromatics). HRMS (ESI+) calculated for C18H23N2O5S [M+H+]: 379.1328. found: 379.1314.

Workup

  1. customThe tetrahydrofuran was evaporated under reduced pressure
  2. customto give an orange syrup
  3. additionwas then added all at once to the above adduct
  4. temperaturethe resulting mixture heated at 60° C. for 3 h
  5. customthe ethanol was evaporated under reduced pressure
  6. additionThe residue was diluted with ethyl acetate
  7. washwashed successively with saturated sodium bicarbonate and brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. washChromatography on silica gel (elution with a gradient of ethyl acetate 20–30% in toluene)

Sources & evidence

ORD record
ord-1f4182a3ba01459cace1437c18272d72
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Reaction notes

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