2-Bromoethyl methyl ether → (2,5-Difluoro-3-{[2-(methyloxy)ethyl]oxy}phenyl)acetonitrile

HRID 253259Notes

Reaction equation

HRID 253259 reaction equation
CC([Si](C)(C)[O:6][C:7]1[C:8]([F:17])=[C:9]([CH2:14][C:15]#[N:16])[CH:10]=[C:11]([F:13])[CH:12]=1)(C)C.[CH3:20][O:21][CH2:22][CH2:23]Br.[F-].[K+]>CN(C=O)C>[F:17][C:8]1[C:7]([O:6][CH2:23][CH2:22][O:21][CH3:20])=[CH:12][C:11]([F:13])=[CH:10][C:9]=1[CH2:14][C:15]#[N:16]

Participants

5

Reactant 3

HCID 809722-Bromoethyl methyl etherHCID 522689Potassium FluorideHCID 66890598(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}-2,5-difluorophenyl)acetonitrile

Product 1

HCID 66889713(2,5-Difluoro-3-{[2-(methyloxy)ethyl]oxy}phenyl)acetonitrileYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,5-difluorophenyl)acetonitrile (1.22 g, 4.30 mmol) in DMF (10 mL) was added 2-bromoethyl methyl ether (485 μl, 5.16 mmol) and potassium fluoride (0.5 g, 8.6 mmol). The mixture was stirred at room temperature for 15 hrs. The reaction mixture was partitioned between ethyl acetate and water. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in-vacuo to afford an orange oil, which was purified by column chromatography. Eluting with 30% ethyl acetate in hexanes gave 690 mg, 3.04 mmol (71%) of (2,5-difluoro-3-{[2-(methyloxy)ethyl]oxy}phenyl)acetonitrile as a colorless oil. 1H NMR (CDCl3): 6.75-6.69 (m, 2H), 4.17-4.15 (m, 2H), 3.78-3.74 (m, 4H), 3.44 (s, 3H); MS (EI) for C11H11NO2F2: 228 (MH+).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. extractionThe aqueous portion was extracted with ethyl acetate
  3. washThe combined organic portion was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in-vacuo
  7. customto afford an orange oil, which
  8. customwas purified by column chromatography
  9. washEluting with 30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3083e5d1bc744add928e49e45d2a4969
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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