Phthalimide → (S)-2-(1-(2-chloro-8-fluoroquinolin-3-yl)ethyl)isoindoline-1,3-dione

Temperature

0 °C

In a round bottomed flask was combined phthalimide (6.38 g, 43.3 mmol), triphenylphosphine (1.14 g, 43.3 mmol), and (R)-1-(2-chloro-8-fluoroquinolin-3-yl)ethanol (8.15 g, 36.2 mmol) in THF (240 mL). The solution was cooled to 0° C. and diisopropylazodicarboxylate (DIAD, 8.5 mL, 43.3 mmol) was added dropwise. The reaction was allowed to warm to rt overnight. The reaction was concentrated to a volume of ˜100 mL and diluted with 1 L of Et2O and 200 mL of water. The layers were separated and the aqueous layer was back extracted with 200 mL of Et2O. The combined organic layers were washed with 160 mL of brine, dried over MgSO4, filtered, and concentrated. Column chromatography using 100% DCM afforded (S)-2-(1-(2-chloro-8-fluoroquinolin-3-yl)ethyl)-isoindoline-1,3-dione (10.5 g, 82% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.60 (br s, 1H), 7.74 (m, 2H), 7.64 (m, 3H), 7.45 (td, J=7.8, 4.9 Hz, 1H), 7.35 (ddd, J=10.2, 7.8, 1.2 Hz, 1H), 5.89 (q, J=7.2 Hz, 1H), 1.90 (d, J=7.0 Hz, 3H).

1. customIn a round bottomed flask was combined
2. temperatureto warm to rt overnight
3. concentrationThe reaction was concentrated to a volume of ˜100 mL
4. additiondiluted with 1 L of Et2O and 200 mL of water
5. customThe layers were separated
6. extractionthe aqueous layer was back extracted with 200 mL of Et2O
7. washThe combined organic layers were washed with 160 mL of brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-5c43934f15c14f7db7d3890983678285

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716290B2