4-Ethoxybenzoic acid → Ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylate

HRID 2068549Notes

Reaction equation

HRID 2068549 reaction equation
[CH2:1]([O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=1)[CH3:2].Cl.[NH2:14][C:15]1([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:17][CH2:16]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>O1CCCC1.C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:14][C:15]2([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:17][CH2:16]2)=[O:10])=[CH:11][CH:12]=1)[CH3:2]

Participants

8

Reactant 5

HCID 120934-Ethoxybenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 58304093Ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylateYield 84%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine 4-ethoxybenzoic acid (10.0 g, 60.18 mmol), ethyl 1-aminocyclopropanecarboxylate hydrochloride (commercially available, 10.96 g, 66.19 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (13.84 g, 72.21 mmol), and 1-hydroxybenzotriazole (HOBT) (9.76 g, 72.21 mmol) in tetrahydrofuran (500 mL). Add diisopropylethylamine (DIEA) (23.09 mL, 132.39 mmol) over 3-5 minutes and stir the reaction for approximately 16 hours at ambient temperature under nitrogen. Dilute the mixture with ethyl acetate, wash with dilute HCl, dilute NaHCO3, and then brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by recrystallization from ethanol to give the title compound (13.93 g, 84%) as a white solid: MS (m/z): 278 (M+1).

Workup

  1. customthe reaction for approximately 16 hours at ambient temperature under nitrogen
  2. washwash with dilute HCl, dilute NaHCO3
  3. dry with materialbrine, dry over sodium sulfate
  4. concentrationconcentrate the organic layer under reduced pressure
  5. customPurify the residue
  6. customby recrystallization from ethanol

Sources & evidence

ORD record
ord-008f6b9919214b72bb5087c69414b622
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

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