Sodium Iodide → Triethyl 1-(acetylamino)heptane-1,1,7-tricarboxylate

HRID 1415163Notes

Reaction equation

HRID 1415163 reaction equation
[O-]CC.[Na+].[C:5]([NH:8][CH:9]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:10]([O:12][CH2:13][CH3:14])=[O:11])(=[O:7])[CH3:6].[I-].[Na+].Br[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]>[Na].O>[C:5]([NH:8][C:9]([C:15]([O:17][CH2:18][CH3:19])=[O:16])([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])(=[O:7])[CH3:6]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 14041Acetamidomalonic acid diethyl esterHCID 122490Ethyl 7-bromoheptanoateHCID 2723922Sodium ethoxide

Product 1

HCID 3017333Triethyl 1-(acetylamino)heptane-1,1,7-tricarboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 5360545SodiumSolvent

Procedure

In a dried flask was dissolved 23.0 g (1.0 g atom) of sodium and 600 ml. of ethanol dried by the method of R. H. Manski, J. Am. Chem. Soc., 53, 1106 (1931). To the solution of sodium ethoxide, under nitrogen, was added 217 g (1.0 mole) of dry diethyl acetamidomalonate and 1.0 g of dry sodium iodide. The resulting solution was heated at reflux while 249 g (1.05 mole) of ethyl 7-bromoheptanoate was added dropwise over a period of 1.5-2 hrs. After addition was completed, the reaction mixture was heated at reflux for 20-24 hrs. By the end of this time a drop of the reaction mixture applied to moist pH paper indicated pH 6-7. The reaction mixture was cooled to room temperature, mixed with 2 liters of water and extracted with ether twice. The combined organic layers were washed with water twice and then with saturated sodium chloride, dried over MgSO4 and evaporated under reduced pressure. The final stage of the evaporation was carried out at 70°-80° to remove last traces of solvent. The remaining oil, which weighed about 363 g, was distilled through a wiped-film molecular still (Rota-Film Molecular Still, All-Starr Scientific Equipment Supply Co., Pompano Beach, Fla.). A foreshot (about 45 g) was collected at about 100°/.01-.005 mm and discarded. Pure triethyl-1-acetamido-1,1,7-heptanetricarboxylate, about 316 g (85%), was then collected at 240°-250°/.005 mm. For other samples prepared similarly: HRMS Calcd for C18H31NO7 m/e 373.2099, measured 373.2078; pmr (CDCl3, TMS) δ1.25 (t, 9H, ethyl CH CH3 's), 2.03 (s, 3H, COCH3), 4.2 (q, 6H, OCH2), 6.95 (s, 1H, NH); ir (neat) 3480 (NH), 1735 (--CO2 --), 1680 (CONH), 1500, 1470, 11450, 1375, 1210 (OC2H5) cm-1.

Workup

  1. dry with materialof ethanol dried by the method of R
  2. temperatureThe resulting solution was heated
  3. additionwas added dropwise over a period of 1.5-2 hrs
  4. additionAfter addition
  5. temperaturethe reaction mixture was heated
  6. temperatureat reflux for 20-24 hrs
  7. extractionextracted with ether twice
  8. washThe combined organic layers were washed with water twice
  9. dry with materialwith saturated sodium chloride, dried over MgSO4
  10. customevaporated under reduced pressure
  11. customThe final stage of the evaporation
  12. customwas carried out at 70°-80°
  13. customto remove last traces of solvent
  14. distillationwas distilled through a wiped-film molecular still (Rota-Film Molecular Still
  15. customA foreshot (about 45 g) was collected at about 100°/.01-.005 mm
  16. customPure triethyl-1-acetamido-1,1,7-heptanetricarboxylate, about 316 g (85%), was then collected at 240°-250°/.005 mm
  17. customFor other samples prepared similarly

Sources & evidence

ORD record
ord-4971352ec1b541ac9f2251dc60b27010
Source dataset
uspto-grants-1977_01
Patent number
US04003911

Reaction notes

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