Hydrochloric Acid → 3-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-phenyl-imidazolidine-4-carboxylic acid methyl ester

HRID 417515Notes

Reaction equation

HRID 417515 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][N:8]([C:10](OC(C)(C)C)=O)[CH2:7][N:6]1[C:17](=[O:27])[CH:18]([NH:22][C:23]([O:25][CH3:26])=[O:24])[CH:19]([CH3:21])[CH3:20])=[O:4].Cl.[C:29]1(B(O)O)[CH:34]=[CH:33]C=[CH:31][CH:30]=1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][N:8]([C:10]2[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=2)[CH2:7][N:6]1[C:17](=[O:27])[CH:18]([NH:22][C:23]([O:25][CH3:26])=[O:24])[CH:19]([CH3:20])[CH3:21])=[O:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 66827Phenylboronic AcidHCID 666211143-(2-Methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester

Product 1

HCID 666208283-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-phenyl-imidazolidine-4-carboxylic acid methyl esterYield 27.2%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

3-(2-Methoxycarbonylamino-3-methyl-butyryl)-imidazolidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl ester (0.20 g, 0.515 mmol) was dissolved in dichloromethane (1.0 mL) and HCl (4M dioxane, 1 mL) was added. The resultant suspension was stirred at room temperature for 60 minutes, after which all volatiles were removed in vacuo. The crude material was combined with phenyl boronic acid (188 mg, 1.545 mmol) and DCM (15 mL) was added. Triethylamine (1.2 mL, 8.89 mmol) was added, followed by copper(II) acetate and molecular sieves 4 Å. The reaction was stirred at room temperature. After 24 hrs, the reaction was quenched with aqueous ammonium hydroxide solution (10%) and the organic layer was isolated. The organic layer was washed with aqueous HCl solution (0.5 M), brine, and was dried over sodium sulfate. Filtration and evaporation gave crude material. Purification via flash chromatography on silica gel (eluent: EtOAc/hexanes) yielded the desired product 3-(2-Methoxycarbonylamino-3-methyl-butyryl)-1-phenyl-imidazolidine-4-carboxylic acid methyl ester (51.0 mg, 0.14 mmol): LCMS-ESI+: calc'd for C18H25N3O5: 363.4 (M+). Found: 364.4 (M+H+).

Workup

  1. customafter which all volatiles were removed in vacuo
  2. additionwas added
  3. customthe reaction was quenched with aqueous ammonium hydroxide solution (10%)
  4. customthe organic layer was isolated
  5. washThe organic layer was washed with aqueous HCl solution (0.5 M), brine
  6. dry with materialwas dried over sodium sulfate
  7. filtrationFiltration and evaporation
  8. customgave crude material
  9. customPurification via flash chromatography on silica gel (eluent: EtOAc/hexanes)

Sources & evidence

ORD record
ord-f02a48beb8f9414cbecafe901671adfa
Source dataset
uspto-grants-2012_01
Patent number
US08088368B2

Reaction notes

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