Water → Methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(3,5-difluorophenyl)propanoate

HRID 23218Notes

Reaction equation

HRID 23218 reaction equation
[NH2:1][C@@H:2]([CH2:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=1)[C:3]([O:5][CH3:6])=[O:4].O.C(=O)([O-])[O-].[Na+].[Na+].[CH2:23]([O:30][C:31](Cl)=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(OCC)(=O)C>[CH2:23]([O:30][C:31]([NH:1][C@@H:2]([CH2:7][C:8]1[CH:9]=[C:10]([F:15])[CH:11]=[C:12]([F:14])[CH:13]=1)[C:3]([O:5][CH3:6])=[O:4])=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 9920793Methyl (2S)-2-amino-3-(3,5-difluorophenyl)propanoate

Product 1

HCID 9968214Methyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(3,5-difluorophenyl)propanoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Methyl (2S)-2-amino-3-(3,5-difluorophenyl)propanoate (XV, EXAMPLE 11, 0.300 g, 1.40 mmol, 1 equivalent) and water (10 mL) are mixed. Sodium carbonate (0.15 g, 1.40 mmol, 1 equivalent) of is added followed by benzylchloroformate (0.2 mL, 0.24 g 1.4 mmol, 1 equivalent) and the mixture stirred at 20-25° until complete as measured by HPLC. Once the reaction is complete, ethyl acetate (20 mL) is added and the phases separated. The aqueous phase is extracted with ethyl acetate (2×20 mL), and the combined organic phases are dried over sodium sulfate, filtered, and concentrated. The concentrate is crystallized from hexanes/ethyl acetate to give the title compound, mp=54°; NMR (DMSO-d6) δ 7.84, 7.28, 7.06, 4.98, 4.35, 3.68, 3.12 and 2.88.

Workup

  1. customthe phases separated
  2. extractionThe aqueous phase is extracted with ethyl acetate (2×20 mL)
  3. dry with materialthe combined organic phases are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrate is crystallized from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-25e58705165a4fe6a709bcb37b121369
Source dataset
uspto-grants-2005_02
Patent number
US06849750B2

Reaction notes

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