Methyl iodide → (S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-nitrophenyl)propanoate

HRID 1976981Notes

Reaction equation

HRID 1976981 reaction equation
[N+:1]([C:4]1[CH:22]=[CH:21][C:7]([CH2:8][C@@H:9]([C:18]([OH:20])=[O:19])[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:23](=O)([O-])[O-].[Na+].[Na+].CI>CN(C=O)C>[CH3:23][O:19][C:18](=[O:20])[C@H:9]([CH2:8][C:7]1[CH:21]=[CH:22][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1)[NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 7021882N-(tert-Butoxycarbonyl)-4-nitro-L-phenylalanine

Product 1

HCID 11558856(S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(4-nitrophenyl)propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-nitro-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine (226.2 mmol, 70.2 g) and sodium carbonate (1.13 mmol, 95 g) in DMF (500 mL) was added methyl iodide (1.13 mmol, 70.4 mL) at room temperature. The suspension was stirred for 15 h at room temperature at this time TLC analysis of the mixture indicated the absence of starting acid and the excess methyl iodide and some DMF were removed under high vacuum. The mixture was poured into water (2 L) and stirred at room temperature as a precipitate formed slowly over weekend. The precipitated solids were collected by filtration and washed with water (2 L). After air and vacuum drying, 72 g (98%) of of 4-nitro-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine methyl ester was isolated as a light yellow solid. mp 95-96° C. 1H NMR, DMSO-d6 (400 MHz) δ8.16 (d, 2H, J=20 Hz), 7.53 (d, 2H, J=20 Hz), 7.39 (d, 1H, J=22 Hz), 4.26-4.28 (m, 1H), 3.6 (s, 3H), 2.96-3.19 (m, 2H), 1.25 (s, 9H), 13C NMR, CDCl3 (100 Mhz) d 172.04, 155.29, 146.27, 145.96, 130.48, 123.18, 78.36, 54.44, 51.9, 36.1, 27.99. HR MS: Obs. mass. 325.1404. Calcd. mass, 325.1400 (M+H).

Workup

  1. customthe excess methyl iodide and some DMF were removed under high vacuum
  2. additionThe mixture was poured into water (2 L)
  3. stirringstirred at room temperature as a precipitate
  4. customformed slowly over weekend
  5. filtrationThe precipitated solids were collected by filtration
  6. washwashed with water (2 L)
  7. customAfter air and vacuum drying

Sources & evidence

ORD record
ord-40c2f98301fc4fe9befa5ec0c3aaccbf
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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