Lithium Hexamethyldisilazide → 1-(3-Bromo-4-fluorophenyl)-2-[4-(2-fluoroethoxy)-phenyl]ethane-1,2-dione

Temperature

-20 °C

A 1.0 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (20 mL, 20 mmol was added at room temperature to a stirred suspension of (3-bromo-4-fluoro-benzyl)triphenylphosphonium bromide (10.6 g, 20 mmol) in tetrahydrofuran (40 mL). The mixture was stirred for 40 minutes, then cooled to −20° C. and treated with 4-(2-fluoroethoxy)benzoyl chloride (4.1 g, 20 mmol) in tetrahydrofuran (40 mL) and stirred for an additional 2 hours while slowly warming to room temperature. The mixture was treated with water (20 mL) and sodium periodate (4.3 g, 20 mmol) then stirred at 50° C. for 18 hours. After cooling to room temperature the mixture was extracted with ethyl acetate. The organic extracts were washed with brine, dried over MgSO4. Evaporation and purification by flash chromatography (hexane/ethyl acetate 9/1) gave a yellow solid (3 g, 41% yield); 1H NMR (400 MHZ, CDCl3) δ 4.25 (m, 1H), 4.32 (m, 1H,) 4.70 (m, 1H), 4.82 (m, 1H), 7.01 (d, 2H), 7.23 (m, 1H), 7.94 (m, 3H), 8.22 (m, 1H); MS m/e (M+CH3COO)− 427; mp 107° C.

1. stirringstirred for an additional 2 hours
2. temperaturewhile slowly warming to room temperature
3. stirringthen stirred at 50° C. for 18 hours
4. temperatureAfter cooling to room temperature the mixture
5. extractionwas extracted with ethyl acetate
6. washThe organic extracts were washed with brine
7. dry with materialdried over MgSO4
8. customEvaporation and purification by flash chromatography (hexane/ethyl acetate 9/1)

ORD record

ord-08627f38e1e14354987226abd3147524

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482349B2