Diisopropylamine → HCID 86585362, compound

Temperature

-78 °C

Under a nitrogen atmosphere, diisopropylamine (2.97 ml, 21.19 mmol) was dissolved in dry tetrahydrofuran (30 ml). After cooling the solution to −78° C., a 1.63 M solution of n-butyllithium in n-hexane (10.8 ml, 17.60 mmol) was added dropwise thereinto over a period of 5 minutes. Then, the liquid reaction mixture was stirred at 0° C. for 15 minutes and cooled to −78° C. Next, a solution (30 ml) of trans 4-(1-ethoxycarbonyl-cyclopropyl)-3-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone (optical isomer B; 4.71 g, 14.13 mmol) in dry tetrahydrofuran was added dropwise thereinto over a period of 5 minutes. The liquid reaction mixture was stirred at −78° C. for 3 minutes. Then, it was added dropwise into a solution (40 ml) of 2,6-di-tert-butylphenol (4.37 g, 21.18 mmol) in dry tetrahydrofuran over a period of 5 minutes. The liquid reaction mixture was stirred at −78° C. for 10 minutes and a saturated aqueous solution of ammonium chloride (200 ml) was added thereto. Next, the liquid reaction mixture was brought back to room temperature and the organic layer was taken up. The aqueous layer was extracted with chloroform (100 ml×2). The combined organic layer was washed with water (100 ml×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was subjected to silica gel columnchromatography to obtain 1.96 g (42%) of the starting compound (eluent: n-hexane:ethyl acetate=2:1) and 1.79 g (38%) of the title compound (eluent:n-hexane:ethyl acetate=3:2) each as an oily substance.

1. customThen, the liquid reaction mixture
2. temperaturecooled to −78° C
3. waitover a period of 5 minutes
4. customThe liquid reaction mixture
5. stirringwas stirred at −78° C. for 3 minutes
6. customThe liquid reaction mixture
7. stirringwas stirred at −78° C. for 10 minutes
8. customNext, the liquid reaction mixture
9. customwas brought back to room temperature
10. extractionThe aqueous layer was extracted with chloroform (100 ml×2)
11. washThe combined organic layer was washed with water (100 ml×2)
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-b487321e776f403c8c683d2684009d13

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06184388B2