Acetamidomalonic acid diethyl ester → Ethyl 3-[2-(3-bromopropyl)phenyl]-2-acetamido-2-carboethoxypropanoate

HRID 542415Notes

Reaction equation

HRID 542415 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].[Br:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22]Br>C(O)C>[Br:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:27]=[CH:26][CH:25]=[CH:24][C:21]=1[CH2:22][C:5]([NH:4][C:1](=[O:3])[CH3:2])([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

4

Reactant 2

HCID 14041Acetamidomalonic acid diethyl esterHCID 202086332-(3-Bromopropyl)benzyl bromide

Product 1

HCID 13922744Ethyl 3-[2-(3-bromopropyl)phenyl]-2-acetamido-2-carboethoxypropanoate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred solution of 0.61 g (27 mmol) Na in 40 mL of dry ethanol was added portionwise 5.86 g (27 mmol) of solid diethyl acetamidomalonate. This mixture was stirred at reflux under nitrogen for 2 h, then cooled to 0°-10° C. on an ice bath. Then, 8.0 g (27 mmol) of 2-(3-bromopropyl)benzyl bromide in 40 mL of dry ethanol was rapidly added. The reaction mixture was stirred for 2 h at 0°-10° C., then 24 h at room temperature. The precipitated inorganic salt was removed by filtration, and was washed with 20 mL of ethanol and discarded. The combined solvents were removed under reduced pressure yielding an orange colored oil. This oil was chromatographed on a column of silica gel with hexane-ethyl acetate (3:1) as eluant. The combined fractions were concentrated under reduced pressure to yield an oil which solidified upon standing, yield 9.5 g (82%), mp 73°-74.5° C. IR(nujol): 1745, 1648 cm-1 (C=O). 1H NMR(D2O) δ 1.3 (t, 6H); 1.9-2.4 (m, 5H); 2.7 (t, 2H); 3.4 (t, 2H); 3.75 (5, 2); 4.3 (q, 4); 6.6 (s, 1H); 7.0-7.3 (m, 4H). Anal Calcd. for C19H26NO3Br: C, 53.28; H, 6.12; N, 3.27; Br, 18.66. Found: C, 53.33; H, 6.13; N, 3.23; Br, 18.67.

Workup

  1. temperatureat reflux under nitrogen for 2 h
  2. temperaturecooled to 0°-10° C. on an ice bath
  3. stirringThe reaction mixture was stirred for 2 h at 0°-10° C.
  4. custom24 h
  5. customat room temperature
  6. customThe precipitated inorganic salt was removed by filtration
  7. washwas washed with 20 mL of ethanol
  8. customThe combined solvents were removed under reduced pressure
  9. customyielding an orange colored oil
  10. customThis oil was chromatographed on a column of silica gel with hexane-ethyl acetate (3:1) as eluant
  11. concentrationThe combined fractions were concentrated under reduced pressure
  12. customto yield an oil which

Sources & evidence

ORD record
ord-03963ab24742422db73369420dd977ad
Source dataset
uspto-grants-1987_04
Patent number
US04657899

Reaction notes

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