Bromide ion → Isohexane ethyl acetate

HRID 2252974Notes

Reaction equation

HRID 2252974 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Mg].[Br-].[CH2:15]([C@@H:17]1[O:19][CH2:18]1)[Cl:16].[Cl-].[NH4+].[CH2:22]([O:24][CH2:25][CH3:26])[CH3:23]>[Cu]I.O>[C:22]([O:24][CH2:25][CH3:26])(=[O:19])[CH3:23].[CH3:3][CH2:4][CH2:5][CH:6]([CH3:8])[CH3:7].[Cl:16][CH2:15][C@H:17]([OH:19])[CH2:18][C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

10

Reactant 6

HCID 259Bromide ionHCID 3283Diethyl Ether3×HCID 25517Ammonium ChlorideHCID 2734062(-)-EpichlorohydrinHCID 27363255-Bromo-2-fluorobenzotrifluorideHCID 5462224Magnesium

Product 2

HCID 21882781Isohexane ethyl acetateYield 5%HCID 58689706HCID 58689706, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Procedure

5-Bromo-2-fluoro-benzotrifluoride (3.16 g, 13 mmol) was added over 5-10 minutes as a solution in diethyl ether (14 mL in total) dropwise to magnesium turnings (0.316 g, 13 mmol) in diethyl ether (1 mL), under an atmosphere of nitrogen. The reaction was maintained at a gentle reflux by control of addition rate during addition of the bromide and then allowed to cool to room temperature and stirred for a further 1 hr. Copper (I) iodide (206 mg, 1.08 mmol) was added in one portion and the reaction mixture cooled to 0° C. over 10 minutes. (R)-epichlorohydrin (1.0 g, 10.8 mmol) was added as a solution in diethyl ether (14 mL in total) over 10 minutes and the reaction allowed to warm to room temperature and stirred for 2 hrs. Ammonium chloride (saturated aqueous solution, 10 mL) and the mixture poured into water (40 mL) and extracted with ethyl acetate (30 mL×2). The combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. Column chromatography (silica; 5% ethyl acetate/isohexane) yielded the desired intermediate (d), (R)-1-chloro-3-(4-fluoro-3-trifluoromethylphenyl)-2-propanol, as a pale yellow oil (3.75 g).

Workup

  1. temperatureThe reaction was maintained at
  2. temperaturethe reaction mixture cooled to 0° C. over 10 minutes
  3. temperatureto warm to room temperature
  4. stirringstirred for 2 hrs
  5. extractionextracted with ethyl acetate (30 mL×2)
  6. washThe combined organic layers were washed with brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e91fb5c0600547b1af6ad2cc84c77974
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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