Acetamidomalonic acid diethyl ester → HCID 13922745, compound

HRID 542419Notes

Reaction equation

HRID 542419 reaction equation
[Na].[C:2]([NH:5][CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])(=[O:4])[CH3:3].Br[CH2:18][CH2:19][CH2:20][C:21]1[CH:35]=[CH:34][CH:33]=[CH:32][C:22]=1[CH2:23][P:24](=[O:31])([O:28][CH2:29][CH3:30])[O:25][CH2:26][CH3:27]>C(O)C.C1(C)C=CC=CC=1>[CH2:29]([O:28][P:24]([CH2:23][C:22]1[CH:32]=[CH:33][CH:34]=[CH:35][C:21]=1[CH2:20][CH2:19][CH2:18][C:6]([NH:5][C:2](=[O:4])[CH3:3])([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([O:25][CH2:26][CH3:27])=[O:31])[CH3:30]

Participants

6

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 5360545SodiumHCID 20208637HCID 20208637, compound

Product 1

HCID 13922745HCID 13922745, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To 0.48 g (21 mmol) of sodium in 50 mL of dry ethanol was added 4.56 g (21 mmol) of solid diethyl acetamidomalonate portionwise. This solution was stirred at reflux under nitrogen for 2 h. After cooling to room temperature the solvent was removed under reduced pressure yielding a tan solid. This solid was dried under vacuum about 2 h. The sodium salt of diethyl acetamidomalonate was then suspended in 50 mL of dry toluene and 9.0 g (21 mmol) of diethyl 2-(3-bromopropyl)benzylphosphonate in 25 mL of dry toluene was added dropwise. This solution was stirred at reflux under nitrogen for 20 h. After cooling to room temperature the solid which precipitated was removed by filtration and washed with toluene. The combined toluene solutions were concentrated under reduced pressure to yield a dark oil. This oil was chromatographed on a column of silica gel with ethyl acetate as eluant. The combined fractions were concentrated under reduced pressure yielding 4.2 g (42%) of the product as a yellow viscous oil which solidified upon standing, mp 76°-79° C. IR(neat) 1745.9, 1680 cm-1 (C=O). 1H NMR(CDCl3) δ 1.0-1.4 (m, 12H); 2.0 (s, 3H); 2.2-3.3 (m, 6H); 3.7-4.4 (m, 8H); 6.8 (5, 1H); 7.0-7.3 (m, 4H). Anal. Calcd. for C23H36NO8P: C, 56.90; H, 7.48; N, 2.89. Found: C, 56.27; H, 7.51; N, 2.86.

Workup

  1. temperatureat reflux under nitrogen for 2 h
  2. customwas removed under reduced pressure
  3. customyielding a tan solid
  4. customThis solid was dried under vacuum about 2 h
  5. stirringThis solution was stirred
  6. temperatureat reflux under nitrogen for 20 h
  7. temperatureAfter cooling to room temperature the solid which
  8. customprecipitated
  9. customwas removed by filtration
  10. washwashed with toluene
  11. concentrationThe combined toluene solutions were concentrated under reduced pressure
  12. customto yield a dark oil
  13. customThis oil was chromatographed on a column of silica gel with ethyl acetate as eluant
  14. concentrationThe combined fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-db751ec68d0d416f95ad7f2668d234a5
Source dataset
uspto-grants-1987_04
Patent number
US04657899

Reaction notes

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