Hydrochloric Acid → Ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylate

HRID 2068524Notes

Reaction equation

HRID 2068524 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)[CH3:8].Cl.[NH2:20][C:21]1([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:23][CH2:22]1.C(N(CC)CC)C.Cl>ClCCl.CN(C)C=O>[CH2:7]([O:9][C:10]1[CH:11]=[CH:12][C:13]([C:14]([NH:20][C:21]2([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:23][CH2:22]2)=[O:16])=[CH:17][CH:18]=1)[CH3:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 120934-Ethoxybenzoic acidHCID 65578Oxalyl chlorideHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochloride

Product 1

HCID 58304093Ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylateYield 95.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

Add oxalyl chloride (189 mL, 2.17 mol) to 4-ethoxybenzoic acid (334.5 g, 1.99 mol) and N,N-dimethylformamide (1 mL) in dichloromethane (3 L). After 1 hr at 25-26° C., concentrate the mixture under reduced pressure until a constant weight is achieved. Stir ethyl 1-aminocyclopropanecarboxylate hydrochloride (300 g, 1.81 mol) and dichloromethane (2.5 L) in an ice water bath. Add triethylamine (631 mL, 4.53 mol) and then add a solution of the acid chloride (ca 380 g) in dichloromethane (500 mL). Stir the reaction mixture for approximately 16 hours at ambient temperature. Dilute the reaction with aqueous 1N hydrochloric acid (1 L). Extract the aqueous layer with dichloromethane (1 L). Wash the organic layer with water (2 L) and brine (2 L). Dry the solution over sodium sulfate, filter, and concentrate under reduced pressure. Slurry the residue in hexanes and filter to give the title compound (478 g, 95%) as an ivory powder: MS (mass spectrometry) (m/z): 278 (M+1).

Workup

  1. concentrationconcentrate the mixture under reduced pressure until a constant weight
  2. additionDilute
  3. extractionExtract the aqueous layer with dichloromethane (1 L)
  4. washWash the organic layer with water (2 L) and brine (2 L)
  5. dry with materialDry the solution over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. filtrationfilter

Sources & evidence

ORD record
ord-2878abc1bb8f47d394014f3bc5ac2ca9
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

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