반응 #76314

반응 방정식

methyl ether

BBr3

3-[[3-(methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy) phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol

→

3-[[3-(bromomethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

수율 59.0%

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   온도warmed to room temperature over 1 hour, at which time HPLC analysis
2. 2
   기타The reaction mixture was quenched with aqueous saturated sodium bicarbonate
3. 3
   workup.ADDITIONdiluted in dichloromethane
4. 4
   세척The organic layer was washed with brine
5. 5
   건조dried over MgSO4
6. 6
   농축concentrated in vacuo
7. 7
   기타The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane 1:7

실험 절차

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) δ3.3 (s, 1H), 3.6 (dd, 1H), 3.9 (dd, 11H), 4.3 (m, 11H), 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).

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