Benzyl chloroformate → rac-Methyl-2-{[(benzyloxy)carbonyl]amino}-6,6,7,7,7-pentafluoroheptanoate

HRID 1844198Notes

Reaction equation

HRID 1844198 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:17])[CH:5]([NH2:16])[CH2:6][CH2:7][CH2:8][C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11].C(=O)([O-])[O-].[K+].[K+].[C:24](Cl)(=[O:33])[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1.O>[CH3:2][O:3][C:4](=[O:17])[CH:5]([NH:16][C:24]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:33])[CH2:6][CH2:7][CH2:8][C:9]([F:14])([F:15])[C:10]([F:11])([F:12])[F:13]

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 90115377Rac-methyl-2-amino-6,6,7,7,7-pentafluoroheptanoate hydrochloride

Product 1

HCID 90115438rac-Methyl-2-{[(benzyloxy)carbonyl]amino}-6,6,7,7,7-pentafluoroheptanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under argon, 16.9 g (59.2 mmol) of rac-methyl-2-amino-6,6,7,7,7-pentafluoroheptanoate hydrochloride (racemate) from Example 139A were initially charged in 775 ml of THF and 99 ml of water, and 25.37 g (183.6 mmol) of potassium carbonate were added carefully at RT. 11.0 ml (65.1 mmol) of benzyl chlorocarbonate were then added dropwise at 0° C., and the suspension was stirred at RT overnight. The reaction mixture was concentrated, water was added to the residue and the mixture was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered and concentrated. The crude product was purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 100/0 to 10/1 to 8/1 to 5/1). The product fraction was then re-purified by preparative RP-HPLC (acetonitrile/water gradient with 0.1% TFA). This gave 13.34 g (56% of theory, purity 94%) of the target compound.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionwater was added to the residue
  3. extractionthe mixture was extracted twice with dichloromethane
  4. dry with materialThe combined organic phases were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (mobile phase: cyclohexane/ethyl acetate gradient: 100/0 to 10/1 to 8/1 to 5/1)
  8. customThe product fraction was then re-purified by preparative RP-HPLC (acetonitrile/water gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-eabc0ccc8bdc43fab3d36f0b283b511f
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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