Ethyl Acetate → 2-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-ureido}-3-methyl-butyric acid methyl ester

HRID 1092314Notes

Reaction equation

HRID 1092314 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(C(O)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C1(P([N:28]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.Cl.[CH3:32][O:33][C:34](=[O:40])[CH:35]([CH:37]([CH3:39])[CH3:38])[NH2:36].[OH-].[Na+].C([O:46][CH2:47]C)(=O)C>C1C=CC=CC=1.C(N(CC)CC)C>[CH3:32][O:33][C:34](=[O:40])[CH:35]([NH:36][C:47]([NH:28][C:8]1([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH2:9][CH2:10]1)=[O:46])[CH:37]([CH3:39])[CH3:38]

Participants

8

Reactant 5

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 199401P,P-Diphenylphosphinic azideHCID 12498813Valine, methyl ester, hydrochloride (1:1)

Product 1

HCID 574956032-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-ureido}-3-methyl-butyric acid methyl ester

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 1-(4-Chlorophenyl)-1-cyclopropane carboxylic acid (400 mg) in benzene (8 mL) was added triethylamine (0.23 mL) and diphenylphosphoryl azide (0.44 mL) over 5 minutes under argon. The mixture was the allowed to stir at 90° C. for 2 hours. D,L-valine methyl ester hydrochloride was added in one portion and stirring was continued at 90° C. for 20 hours. The mixture was cooled and added to ethyl acetate and 1 M NaOH. The layers were separated and the organic phase was washed with brine, dried over Na2SO4 and evaporated. The residue was purified by flash chromatography using methanol/ethyl acetate 9:1 as an eluent. Fractions containing the desired material were combined and evaporated to give 2-{3-[1-(4-chloro-phenyl)-cyclopropyl]-ureido}-3-methyl-butyric acid methyl ester as colorless solid (500 mg). MS (ESI): 325.2 (MH+).

Workup

  1. stirringstirring
  2. waitwas continued at 90° C. for 20 hours
  3. temperatureThe mixture was cooled
  4. customThe layers were separated
  5. washthe organic phase was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customThe residue was purified by flash chromatography
  9. additionFractions containing the desired material
  10. customevaporated

Sources & evidence

ORD record
ord-264d6b9a681d4f06a5c5b3fcb2b8be9b
Source dataset
uspto-grants-2012_03
Patent number
US08129423B2

Reaction notes

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