Diethylamine → N,N-diethyl-4-formylbenzamide

HRID 1795905Notes

Reaction equation

HRID 1795905 reaction equation
[C:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][CH:5]=1)([OH:3])=O.[CH2:12]([N:14](CC)[CH2:15][CH3:16])[CH3:13].C(Cl)(=O)C(C)(C)C.C(NCC)C>O1CCCC1>[CH:8]([C:7]1[CH:10]=[CH:11][C:4]([C:1]([N:14]([CH2:15][CH3:16])[CH2:12][CH3:13])=[O:3])=[CH:5][CH:6]=1)=[O:9]

Participants

6

Reactant 4

HCID 8021DiethylamineHCID 8471TriethylamineHCID 120884-Formylbenzoic acidHCID 62493Pivaloyl chloride

Product 1

HCID 10954698N,N-diethyl-4-formylbenzamideYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-4 °C

Procedure

To a 12 L flask equipped with mechanical stirrer and cold bath was charged 300 g (2 mol) of 4-carboxybenzaldehyde, 4.5 L of tetrahydrofuran and 245 g (2.4 mol) of triethylamine. This solution was cooled to −4° C. with methanol/ice bath. To the reaction was charged 236 g (1.9 mol) of pivaloyl chloride at a rate that maintained the temperature below 5° C. After stirring for 2 h the resulting slurry was filtered and the filter cake was washed with 1 L of THF. The filtrates were returned to the reactor and cooled below −5° C. Diethylamine (438 g, 6 mol) was slowly added maintaining the temperature below 0° C. The reaction was stirred for several hours and allowed to warm. The solvent was then removed under vacuum and the resulting residue was dissolved in 2 L of ethyl acetate. The resulting solution was washed with 1 L of water and the aqueous layer was back-extracted with 2×500 mL ethyl acetate. The combined organic layer was washed with 3×500 mL of 1 N HCl and 3×500 mL of NaHCO3 (aq, sat). This solution was dried with Na2SO4 and the solvent was removed under vacuum to give a golden brown oil (172 g, 85%) containing ˜13% impurity by NMR. The aldehyde was used with out further purification.

Workup

  1. customTo a 12 L flask equipped with mechanical stirrer and cold bath
  2. temperaturemaintained the temperature below 5° C
  3. filtrationwas filtered
  4. washthe filter cake was washed with 1 L of THF
  5. temperaturecooled below −5° C
  6. temperaturemaintaining the temperature below 0° C
  7. stirringThe reaction was stirred for several hours
  8. temperatureto warm
  9. customThe solvent was then removed under vacuum
  10. dissolutionthe resulting residue was dissolved in 2 L of ethyl acetate
  11. washThe resulting solution was washed with 1 L of water
  12. extractionthe aqueous layer was back-extracted with 2×500 mL ethyl acetate
  13. washThe combined organic layer was washed with 3×500 mL of 1 N HCl and 3×500 mL of NaHCO3 (aq, sat)
  14. dry with materialThis solution was dried with Na2SO4
  15. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-225b749de37643cfb46663b3eb6f7940
Source dataset
uspto-grants-2006_04
Patent number
US07030124B2

Reaction notes

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