Acetic Acid → Tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamate

HRID 922533Notes

Reaction equation

HRID 922533 reaction equation
ClC(Cl)(Cl)COC(=O)[NH:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]2[CH2:15][C@H:14]2[N:16]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:18]2[CH2:20][CH2:19]2)=[CH:9][CH:8]=1.C(O)(=O)C.[OH-].[Na+].C(OCC)(=O)C>C1COCC1.[Zn]>[NH2:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]2[CH2:15][C@H:14]2[N:16]([CH2:17][CH:18]2[CH2:20][CH2:19]2)[C:21](=[O:22])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 1317349732,2,2-Trichloroethyl(4-{trans-2-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]cyclopropyl}phenyl)-carbamate

Product 1

HCID 86729891Tert-butyl [trans-2-(4-aminophenyl)cyclopropyl](cyclopropylmethyl)carbamateYield 67.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,2,2-trichloroethyl(4-{trans-2-[(tert-butoxycarbonyl)(cyclopropylmethyl)amino]cyclopropyl}phenyl)-carbamate (15.9 g) in THF (166 mL) were added zinc powder (32.6 g) and acetic acid (5 mL). The reaction mixture was stirred at room temperature for 5 hr, 1N aqueous sodium hydroxide solution (100 mL) and ethyl acetate (500 mL) were added, and the mixture was filtered through celite. The organic layer was separated from the mother liquor, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate) to give the title compound (6.83 g).

Workup

  1. filtrationthe mixture was filtered through celite
  2. customThe organic layer was separated from the mother liquor
  3. washwashed successively with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f77d6eee972647f89dc22eb1fbcfbc70
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

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