Reaction #162535

Reaction equation

diisopropylazodicarboxylate

phthalimide

triphenylphosphine

(R)-1-(2-chloro-8-fluoroquinolin-3-yl)ethanol

→

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

Yield 82.0%

Solvents

THF

Conditions

Workup

1. 1
   OtherIn a round bottomed flask was combined
2. 2
   Temperatureto warm to rt overnight
3. 3
   ConcentrationThe reaction was concentrated to a volume of ˜100 mL
4. 4
   workup.ADDITIONdiluted with 1 L of Et2O and 200 mL of water
5. 5
   OtherThe layers were separated
6. 6
   Extractionthe aqueous layer was back extracted with 200 mL of Et2O
7. 7
   WashThe combined organic layers were washed with 160 mL of brine
8. 8
   Dryingdried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated

Procedure

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).

Source