Dimethyl Ether → 3-[[3-(Bromomethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

Temperature

-50 °C

EX-514D) The 3-[[3-(methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol from EX-514C (1 g, 2.2 mmol) was dissolved in 10 mL of dichloromethane. The solution was cooled to −50° C. and a 1 M solution of BBr3 in dichloromethane (2.3 mL, 2.3 mmol) was added. The solution was stirred at −50° C. for 1 hour and warmed to room temperature over 1 hour, at which time HPLC analysis indicated that no methyl ether starting material remained. The reaction mixture was quenched with aqueous saturated sodium bicarbonate and diluted in dichloromethane. The organic layer was washed with brine, then dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane 1:7 to give 0.65 g (59%) of the desired 3-[[3-(bromomethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a brown oil. HRMS calcd. for C19H18BrF7NO2: 504.0409 [M+H]+, found: 504.0361. 1H NMR (CDCl3) δ 3.3 (s, 1H), 3.6 (dd, 1H), 3.9 (dd, 1H), 4.3 (m, 1H), 4.4 (s, 2H), 4.8 (m, 2H), 5.9 (tt, 1H), 6.7 (d, 1H), 6.8-6.9 (m, 2H), 7.1-7.3 (m, 4H), 7.4 (t, 1H).

1. temperaturewarmed to room temperature over 1 hour, at which time HPLC analysis
2. customThe reaction mixture was quenched with aqueous saturated sodium bicarbonate
3. additiondiluted in dichloromethane
4. washThe organic layer was washed with brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane 1:7

ORD record

ord-877dc64ef06b4486b88a62f660dc04bf

Source dataset

uspto-grants-2004_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06677382B1