Benzyl Bromide → 3-(4-Bromophenyl)-2,2-bis(3-(trifluoromethoxy)phenyl)propanoic acid

Temperature

-40 °C

To a solution of 2,2-bis(3-(trifluoromethoxy)phenyl)acetic acid (198 mg, 0.52 mmol) in THF (3.5 mL) at −15° C. was added dropwise a 1.6 M solution of nBuLi in hexanes (0.65 mL, 1.04 mmol). The reaction mixture was stirred for 45 min. The solution was cooled to −40° C. and a solution of benzylbromide (130 mg, 0.52 mmol) in THF (0.6 mL) was added dropwise. The ice-bath was removed and the reaction mixture was allowed to warm up to rt. The reaction was quenched by addition of sat. NH4Cl (5 mL) and extracted with Et2O (3×5 mL). The combined organic portions were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica chromatography, eluting with 30% EtOAc/hexane containing 1% AcOH to give 3-(4-bromophenyl)-2,2-bis(3-(trifluoromethoxy)phenyl)propanoic acid (232 mg, 81% yield) as a clear colorless oil. LCMS: RT=1.93 min [M+H] 549.0 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) δ ppm 3.62 (s, 2H), 6.53 (d, J=8.35 Hz, 2H), 7.04 (s, 2H), 7.10 (d, J=7.91 Hz, 2H), 7.13-7.19 (m, 4H), 7.30 (t, J=8.13 Hz, 2H).

1. customThe ice-bath was removed
2. temperatureto warm up to rt
3. customThe reaction was quenched by addition of sat. NH4Cl (5 mL)
4. extractionextracted with Et2O (3×5 mL)
5. dry with materialThe combined organic portions were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica chromatography
9. washeluting with 30% EtOAc/hexane containing 1% AcOH

ORD record

ord-a313cca26b9d486489b0e2b22c6d79c2

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642576B2