Dichloromethane → N-(N'-BOC-aminoethyl)-N-[(1-thyminyl)-propanoyl]glycine ethyl ester

HRID 1976803Notes

Reaction equation

HRID 1976803 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][NH:6][CH2:7][CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH3:2].[N:18]1([CH2:27][CH2:28][C:29](O)=[O:30])[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]1=[O:20].C(Cl)Cl.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][N:6]([CH2:7][CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:29](=[O:30])[CH2:28][CH2:27][N:18]1[CH:26]=[C:24]([CH3:25])[C:22](=[O:23])[NH:21][C:19]1=[O:20])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10868DicyclohexylcarbodiimideHCID 15195633-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propanoic acidHCID 4319362Ethyl N-{2-[(tert-butoxycarbonyl)amino]ethyl}glycinate

Product 1

HCID 86595832N-(N'-BOC-aminoethyl)-N-[(1-thyminyl)-propanoyl]glycine ethyl esterYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-(N′-Boc-aminoethyl)glycine ethyl ester (1.0 g, 0.0041 mol) was dissolved in DMF (12 ml). DhbtOH (0.73 g, 0.0045 mol) and 3-(1-thyminyl)-propanoic acid (0.89 g, 0.0045 mol) were added. Methylene chloride (12 ml) then was added and the mixture was cooled to 0° C. on an ice bath. After addition of DCC (1.01 g, 0.0049 mol), the mixture was stirred at 0° C. for 2 h, followed by 1 h at room temperature. The precipitated DCU was removed by filtration, washed with methylene chloride (25 ml), and a further amount of methylene chloride (50 ml) was added to the filtrate. The organic phase was extracted with sodium hydrogen carbonate (1 volume saturated diluted with 1 volume water, 6×100 ml), potassium sulfate (1 volume saturated diluted with 4 volumes water, 3×100 ml), and saturated aqueous sodium chloride (1×100 ml), dried over magnesium sulfate, and evaporated to dryness, in vacuo. The solid residue was suspended in methylene chloride (15 ml), and stirred for 1 h. The precipitated DCU was removed by filtration and washed with methylene chloride. The filtrate was evaporated to dryness, in vacuo, and the residue purified by column chromatography on silica gel, eluting with a mixture of methanol and methylene chloride (gradient from 1 to 6% methanol in methylene chloride). This afforded the title compound as a white solid (1.02 g, 59%). Anal. for C19H30N4O7, found (calc.) C: 53.15 (53.51) H: 6.90 (7.09) N: 12.76 (13.13). The compound showed satisfactory 1H and 13C-NMR spectra.

Workup

  1. waitfollowed by 1 h at room temperature
  2. customThe precipitated DCU was removed by filtration
  3. washwashed with methylene chloride (25 ml)
  4. additiona further amount of methylene chloride (50 ml) was added to the filtrate
  5. extractionThe organic phase was extracted with sodium hydrogen carbonate (1 volume saturated diluted with 1 volume water, 6×100 ml), potassium sulfate (1 volume saturated diluted with 4 volumes water, 3×100 ml), and saturated aqueous sodium chloride (1×100 ml)
  6. dry with materialdried over magnesium sulfate
  7. customevaporated to dryness, in vacuo
  8. stirringstirred for 1 h
  9. customThe precipitated DCU was removed by filtration
  10. washwashed with methylene chloride
  11. customThe filtrate was evaporated to dryness, in vacuo
  12. customthe residue purified by column chromatography on silica gel
  13. washeluting with a mixture of methanol and methylene chloride (gradient from 1 to 6% methanol in methylene chloride)

Sources & evidence

ORD record
ord-cf8e36cb04ef4a358784c12d57c19fee
Source dataset
uspto-grants-2001_05
Patent number
US06228982B1

Reaction notes

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