Hexane → {(1S,2S,4S)-1-[4-(2-Chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-ylmethyl]-2-hydroxy-5-methyl-4-(2,2,2-trifluoroethyl)carbamoylhexyl}carbamic acid t-butyl ester

2 ml of a solution of dimethylaluminum chloride in n-hexane (1.0 mol/l) (2 mmol) was added to a solution of 160 μl of (2,2,2-trifluoroethyl)amine (2 mmol) in methylene chloride under a nitrogen atmosphere at room temperature, and the mixture was stirred at room temperature for one hour. A solution of 200 mg of {(S)-2-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-1-[(2S,4S)-4-isopropyl-5-oxotetrahydrofuran-2-yl]ethyl}carbamic acid t-butyl ester obtained in Example (1m) (0.39 mmol) in methylene chloride (4 ml) was added to the solution obtained above, and the mixture was stirred at room temperature for 26 hours. A 10% potassium sodium tartrate aqueous solution was added to the reaction mixture, followed by dilution with ethyl acetate. Then, the mixture was stirred at room temperature for 0.5 hour. The reaction mixture was extracted with ethyl acetate, and then the organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=40/1) to obtain 132 mg of the title compound (yield: 55%).

1. customobtained above, and the mixture
2. stirringwas stirred at room temperature for 26 hours
3. stirringThen, the mixture was stirred at room temperature for 0.5 hour
4. extractionThe reaction mixture was extracted with ethyl acetate
5. washthe organic layer was washed with brine
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationAfter filtration
8. customthe solvent was evaporated under reduced pressure
9. customthe residue was purified by silica gel column chromatography (elution solvent:methylene chloride/methanol=40/1)

ORD record

ord-5c850cb3c91746e3b9cab3a5e8ef19aa

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158790B2