Methanol → 4-Amino-N-((1,1-dimethylethoxy)carbonyl)-L-phenylalanine methyl ester

HRID 63715Notes

Reaction equation

HRID 63715 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C@@:4](C)([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][CH:7]=1.[Cl-].[NH4+].CO>[Zn].O>[CH3:1][O:2][C:3](=[O:24])[C@@H:4]([NH:15][C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 86691348methyl (S)-3-[4-nitrophenyl]-2-tert-butoxycarbonylamino-propionic acid methyl ester

Product 1

HCID 110118554-Amino-N-((1,1-dimethylethoxy)carbonyl)-L-phenylalanine methyl esterYield 100.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent2×

Procedure

To a mixture of methyl (S)-3-[4-nitrophenyl]-2-tert-butoxycarbonylamino-propionic acid methyl ester (72 g, 222 mmol), zinc dust (˜325 mesh, 145.2 g, 2.2 mole, 10 equiv.) and ammonium chloride (178.1 g, 3.3 mole, 15 equiv.) was added methanol (1 L) and water (500 mL) at room temperature. After addition of water, an exothermic reaction ensued and the internal temperature rose to 45 to 50° C. The suspension was stirred for 30 min to 1 h at room temperature, at which time TLC analysis of the mixture indicated the absence of starting material, and the reaction mixture was filtered through a pad of celite and the filtered cake was washed with methanol (1 L) and water (500 mL). Concentration to remove most of the methanol and some water afforded white solids which were collected by filtration and washed with water. After air drying, 65.5 g (100% yield) of (S)-3-[4-aminophenyl]-2-tert-butoxycarbonylamino-propionic acid methyl ester was isolated as a white solid (mp 86-89° C.). ES(+)-HRMS m/e calcd. for C15H22N2O4 (M+H)+ 294.1621, obsd. 294.1614.

Workup

  1. customan exothermic reaction
  2. customrose to 45 to 50° C
  3. filtrationthe reaction mixture was filtered through a pad of celite
  4. washthe filtered cake was washed with methanol (1 L) and water (500 mL)
  5. concentrationConcentration
  6. customto remove most of the methanol
  7. filtrationsome water afforded white solids which were collected by filtration
  8. washwashed with water
  9. customAfter air drying

Sources & evidence

ORD record
ord-74f2e889bed241a7ac483daaaffe3fed
Source dataset
uspto-grants-2016_09
Patent number
US09447035B2

Reaction notes

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