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

HRID 1017054Notes

Reaction equation

HRID 1017054 reaction equation
CO[CH2:3][C:4]1[CH:5]=[C:6]([N:10]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])[CH:20]=2)[CH2:11][CH:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH:7]=[CH:8][CH:9]=1.B(Br)(Br)[Br:33].COC>ClCCl>[Br:33][CH2:3][C:4]1[CH:5]=[C:6]([N:10]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:31])([F:30])[CH:27]([F:29])[F:28])[CH:20]=2)[CH2:11][CH:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 8254Dimethyl EtherHCID 25134Boron tribromideHCID 235060003-[[3-(Methoxymethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol

Product 1

HCID 235060603-[[3-(Bromomethyl)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

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, 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).

Workup

  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

Sources & evidence

ORD record
ord-cb5bb005749e407e9b1e5360dd1b54b3
Source dataset
uspto-grants-2002_11
Patent number
US06476075B1

Reaction notes

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