Guanidine Hydrochloride → HCID 136028598, compound

HRID 458687Notes

Reaction equation

HRID 458687 reaction equation
[C:1](OCC)(=O)[C:2]([O:4][CH2:5][CH3:6])=[O:3].[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+].[O-]CC.[Na+].Cl.[NH2:32][C:33]([NH2:35])=[NH:34]>O1CCCC1.C(O)C.C(O)(=O)C>[CH2:5]([O:4][C:2]([C:1]1[N:32]=[C:33]([NH2:35])[NH:34][C:20](=[O:22])[C:19]=1[O:18][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:3])[CH3:6]

Participants

9

Reactant 5

HCID 5742Guanidine HydrochlorideHCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 290299Ethyl 2-(benzyloxy)acetateHCID 2723922Sodium ethoxide

Product 1

HCID 136028598HCID 136028598, compoundYield 5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

A solution of diethyl oxalate (21.06 g, 0.144 mol) and ethyl benzyloxyacetate (28.0 g, 0.144 mol) in dry tetrahydrofuran (200 ml) was treated at 22° C. with sodium hydride (6.34 g of a 60% dispersion in mineral oil, 0.158 mol). Ethanol (0.05 ml) was added and the resulting mixture stirred at 22° C. for 18 h. The tetrahydrofuran was then evaporated under reduced pressure and the residual orange syrup dissolved in a solution of sodium ethoxide (0.144 mol, prepared from 3.31 g of sodium) in ethanol (200 ml). Guanidine hydrochloride (14.6 g, 0.153 mol) was added and the resulting mixture heated at 60° C. for 7 h. Acetic acid (3 ml) was then added to the gel-like reaction mixture and the ethanol was removed under reduced pressure. The residual paste was triturated with a mixture of ethyl alcohol and dichloromethane (1:4), filtered and the filtrate concentrated under reduced pressure. Chromatography of the residue on silica gel (elution with a gradient of ethyl alcohol 0–15% in dichloromethane) followed by recrystallization from 1,2-dichloroethane gave 2.00 g (5% yield) of the title ester as a yellow solid. 1HNMR 400 MHz (DMSO-d6) δ (ppm): 1.18 (3H, t, J=7.0 Hz, CH3), 4.17 (2H, q, J=7.0 Hz, CH2), 4.90 (2H, s, OCH2), 6.55 (2H, broad s, NH2), 7.3–7.4 (5H, m, aromatics), 11.4 (1H, broad s, NH). Anal. Calcd for C14H15N3O4: C, 58.12; H, 5.22; N, 14.52. Found: C, 57.94; H, 5.11; N, 14.58.

Workup

  1. customThe tetrahydrofuran was then evaporated under reduced pressure
  2. temperaturethe resulting mixture heated at 60° C. for 7 h
  3. customthe ethanol was removed under reduced pressure
  4. customThe residual paste was triturated with a mixture of ethyl alcohol and dichloromethane (1:4)
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. washChromatography of the residue on silica gel (elution with a gradient of ethyl alcohol 0–15% in dichloromethane)
  8. customfollowed by recrystallization from 1,2-dichloroethane

Sources & evidence

ORD record
ord-4752468876224fd6a1619d1b8f9c991a
Source dataset
uspto-grants-2007_03
Patent number
US07192948B2

Reaction notes

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