Reaction #1833219

Reaction equation

1,1,2-Trichloro-1,2,2-trifluoroethane

2,2,6,6-Tetramethylpiperidine

n-butyllithium

NH4Cl

5-Bromo-2,2-difluorobenzo[d][1,3]dioxole

→

title compound

Yield 28.1%

5-Bromo-4-chloro-2,2-difluorobenzo[d][1,3]dioxole

Yield 28.1%

Solvents

water

diethyl ether

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred for 2 h at −75° C
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued for 1.5 h
4. 4
   WashThe ether phase was washed with saturated NaCl (10 mL)
5. 5
   Dryingdried (Na2SO4)
6. 6
   Otherevaporated under vacuum
7. 7
   OtherThe residue was purified by chromatography on silica with hexane
8. 8
   Otherrepurified by reverse-phase

Procedure

2,2,6,6-Tetramethylpiperidine (2.1 mL, 1.8 g, 12 mmol) was dissolved in dry tetrahydrofuran (15 mL), cooled to −75° C. and treated with n-butyllithium (n-BuLi, 2.5 M; 4.8 mL, 12 mmol), and the mixture was stirred for 30 min at −75° C. 5-Bromo-2,2-difluorobenzo[d][1,3]dioxole (2.0 g, 8.4 mmol) was added, and the mixture was stirred for 2 h at −75° C. 1,1,2-Trichloro-1,2,2-trifluoroethane (2.4 mL, 3.8 g, 20 mmol) was added and stirring was continued for 1.5 h. Saturated NH4Cl (10 mL) was added, and the mixture was shaken with diethyl ether (30 mL) and water (20 mL). The ether phase was washed with saturated NaCl (10 mL), dried (Na2SO4) and evaporated under vacuum. The residue was purified by chromatography on silica with hexane and then repurified by reverse-phase HPLC using 75% acetonitrile to give the title compound as a clear liquid (640 mg, 28%): 1H NMR (400 MHz, CDCl3) δ 7.38 (dd, J=8.5, 5.1 Hz, 1H), 6.90 (dd, J=9.0, 4.7 Hz, 1H); EIMS m/z 332.

Source