Benzyl chloroformate → HCID 57446950, compound

HRID 1880522Notes

Reaction equation

HRID 1880522 reaction equation
[F:1][C:2]([F:12])([F:11])[CH:3]([CH3:10])[CH2:4][C@@H:5]([C:7]([OH:9])=[O:8])[NH2:6].Cl[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].[OH-].[Na+]>O>[CH2:17]([O:16][C:14]([NH:6][C@H:5]([C:7]([OH:9])=[O:8])[CH2:4][CH:3]([C:2]([F:11])([F:12])[F:1])[CH3:10])=[O:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 14798Sodium HydroxideHCID 1645875,5,5-trifluoro-l-leucine

Product 1

HCID 57446950HCID 57446950, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the 5,5,5-trifluoro-L-leucine (12 g) in H2O (150 mL) at 0° C. was added benzyl chloroformate (4.8 mL, 34 mol), followed by dropwise addition of 1 M aqueous NaOH (120 mL, 120 mmol). More benzyl chloroformate (4.8 mL, 34 mmol) was added. The mixture was further stirred at 0° C. and the pH of the mixture became ˜7. The mixture was washed with Et2O (2×) and acidified with aqueous HCl. The aqueous layer was extracted with EtOAc (3×), dried (Na2SO4) and concentrated in vacuo to provide N-[(benzyloxy)carbonyl]-5,5,5-trifluoro-L-leucine. The crude acid was dissolved in Et2O and treated with a solution of diazomethane in Et2O. Chromatography over silica gel and elution with hexanes:Et2O (7:3) gave methyl (4S)—N-[(benzyloxy)carbonyl]-5,5,5-trifluoro-L-leucinate as the less polar fraction.

Workup

  1. washThe mixture was washed with Et2O (2×)
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5a4990e2d80746a4bfbb65be8bbb82e6
Source dataset
uspto-grants-2012_11
Patent number
US08318748B2

Reaction notes

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