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

HRID 393486Notes

Reaction equation

HRID 393486 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[Cl-].[NH4+].CO>[Zn].O>[CH3:1][O:2][C:3](=[O:23])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7]

Participants

6

Reactant 3

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 11558856(S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-nitrophenyl)propanoate

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 of N-[(1,1-dimethylethoxy)carbonyl]-4-nitro-L-phenylalanine methyl ester (222 mmol, 72 g), zinc dust (˜325 mesh, 2.2 mol, 145.2 g, 10 equiv) and ammonium chloride (3.3 mol, 178.1 g, 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 afforded white solid which was collected by filtration and washed with water. After air drying, 65.5 g of a white solid, mp 86-89° C. was obtained. 1H-NMR (DMSO-d6) (400 MHz) δ 6.9 (d, 2H, J=20 Hz), 6.62 (d, 2H, J=20 Hz), 7.39 (d, 1H, J=22 Hz), 4.26-4.28 (m, 1H), 3.68 (s, 3H), 2.96-3.19 (m, 2H), 1.25 (s, 9H). HR MS: Obs. mass, 294.1614. Calcd. mass, 294.1621 (M+).

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 afforded white solid which
  7. filtrationwas collected by filtration
  8. washwashed with water
  9. customAfter air drying

Sources & evidence

ORD record
ord-89f625eb15a8484f9ae1fd72db88fef3
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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