Reaction #607496

Reaction equation

NaOH

methanesulfonic acid

144d

5-bromo-7-fluoro-2,3-dihydro-1H-inden-1-one

sodium azide

→

6-bromo-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one

Yield 47.1%

Solvents

DCM

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was stirred for 30 min
2. 2
   Extractionthe aqueous phase was extracted with DCM (400 mL×3)
3. 3
   WashThe combined organic layers were washed with saturated brine (200 mL×2)
4. 4
   Dryingdried with anhydrous sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   OtherThe residue was purified by silica gel chromatography (PE/EA=10/1 to 2/1)

Procedure

To a mixture of 144d (10.35 g, 45.19 mmol) in DCM (75 mL) was added methanesulfonic acid (52.73 mL, 70.92 g, 737.90 mmol) at 0° C., followed by sodium azide (5.88 g, 90.44 mmol) in several portions. See FIG. 3. The reaction mixture was stirred at 0° C. for 2 h, and 20% aq. NaOH solution (40 mL) was added. The reaction mixture was stirred for 30 min, and the aqueous phase was extracted with DCM (400 mL×3). The combined organic layers were washed with saturated brine (200 mL×2), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE/EA=10/1 to 2/1) to afford the 5.2 g (47.1%) of 6-bromo-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one 144e. 1H NMR (400 MHz, CDCl3) δ 7.22-7.25 (d, J=10.4 Hz, 1H), 7.20 (s, 1H), 6.94 (s, 1H), 3.46-3.53 (m, 2H), 2.88-2.97 (m, 2H); MS-ESI [M+H]+=243.9/245.9.

Source