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

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.

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)

ORD record

ord-eabc0ccc8bdc43fab3d36f0b283b511f

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946215B2