Benzyl chloroformate → rac-Methyl N-[(benzyloxy)carbonyl]-5,5,6,6,6-pentafluoronorleucinate

HRID 1844196Notes

Reaction equation

HRID 1844196 reaction equation
Cl.[F:2][C:3]([F:16])([C:12]([F:15])([F:14])[F:13])[CH2:4][CH2:5][C@@H:6]([C:8]([O:10][CH3:11])=[O:9])[NH2:7].C(=O)([O-])[O-].[K+].[K+].Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C1COCC1.O>[CH2:27]([O:26][C:24]([NH:7][C@H:6]([C:8]([O:10][CH3:11])=[O:9])[CH2:5][CH2:4][C:3]([F:16])([F:2])[C:12]([F:13])([F:14])[F:15])=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 90115167rac-Methyl 5,5,6,6,6-pentafluoronorleucinate hydrochloride

Product 1

HCID 90115375rac-Methyl N-[(benzyloxy)carbonyl]-5,5,6,6,6-pentafluoronorleucinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon, 141.5 g (520.99 mmol) of rac-methyl 5,5,6,6,6-pentafluoronorleucinate hydrochloride from Example 133A were taken up in 850 ml of THF and 850 ml of water, and 223.2 g (1.62 mol) of potassium carbonate were added carefully at RT. 82 ml (573.09 mmol) of benzyl chloroformate were then added dropwise, and the suspension was stirred at RT overnight. The reaction mixture was extracted twice with 500 ml of ethyl acetate and the organic phase was dried with magnesium sulphate, filtered off and concentrated. The residue was diluted with 50 ml of dichloromethane and purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 9/1 to 4/1). The isolated product fraction was re-purified by preparative HPLC [Daiso C18 10 μm Bio 300×100 mm, neutral; mobile phase: acetonitrile/water gradient; flow rate: 250 ml/min; temperature: RT; wave length: 210 nm). This gave 27.4 g (14% of theory) of the target compound.

Workup

  1. extractionThe reaction mixture was extracted twice with 500 ml of ethyl acetate
  2. dry with materialthe organic phase was dried with magnesium sulphate
  3. filtrationfiltered off
  4. concentrationconcentrated
  5. additionThe residue was diluted with 50 ml of dichloromethane
  6. custompurified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 9/1 to 4/1)
  7. customThe isolated product fraction was re-purified by preparative HPLC [Daiso
  8. customRT

Sources & evidence

ORD record
ord-6f83f272613e41d7867871b42ee09c49
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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