Acetamidomalonic acid diethyl ester → HCID 10547728, compound

HRID 2120120Notes

Reaction equation

HRID 2120120 reaction equation
[C:1]([NH:4][CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].CC[O-].[Na+].Cl[CH2:21][CH2:22][C:23]([C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:26]=1[OH:32])=[O:24]>CCO>[C:1]([NH:4][C:5]([CH2:21][CH2:22][C:23]([C:25]1[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:26]=1[OH:32])=[O:24])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 2723922Sodium ethoxideHCID 107031382-(3-Chloropropionyl)-4-methylphenol

Product 1

HCID 10547728HCID 10547728, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Diethyl acetamidomalonate (12.84 g, 59.11 mmol) was added to freshly prepared 0.29 M NaOEt (225 ml) in EtOH at 0° C. The solution resulting after brief sonication was transferred to an addition funnel and added over six minutes to a suspension of 20 (10.68 g, 53.74 mmol) in EtOH (50 ml) at 0° C. After stirring the reaction mixture for 18 hours at room temperature, solvent was removed in vacuo. Cold 0.25 N HCl (200 ml) was added and the aqueous phase was extracted with CHCl3 (200 ml, 2×100 ml). The organic layer was washed with H2O (100 ml). After solvent removal, the solid was purified by silica gel flash column chromatography using 4% acetone/—CH2Cl2 to furnish 18.1 g (89%) of diethyl (acetylamino)[3-(2—hydroxy-5-methylphenyl)-3-oxopropyl]propanedioate (I) as a solid: NMR δ 1.26 (t, 6H, J=7), 2.04 (s, 3H), 2.30 (s, 3H), 2.78 (t, 2H, J=7), 2.98 (t, 2H, J=7), 4.17-4.34 (m, 4H), 6.79 (s, 1H), 6.88 (d, 1H, J=8), 7.25-7.30 (m, 1H), 7.47 (s, 1H), 11.97 (s, 1H). Anal. calcd. for C19H25NO7: C 60.15, H 6.64, N 3.69. Found: C 60.23, H 6.73, N 3.77.

Workup

  1. customThe solution resulting
  2. customafter brief sonication
  3. customwas transferred to an addition funnel
  4. customsolvent was removed in vacuo
  5. additionCold 0.25 N HCl (200 ml) was added
  6. extractionthe aqueous phase was extracted with CHCl3 (200 ml, 2×100 ml)
  7. washThe organic layer was washed with H2O (100 ml)
  8. customAfter solvent removal
  9. customthe solid was purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-c7888b1a499e48928970ae289634ea87
Source dataset
uspto-grants-2004_02
Patent number
US06689788B1

Reaction notes

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