Chloromethyl Methyl Ether → HCID 66889518, compound

HRID 253260Notes

Reaction equation

HRID 253260 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.[F-].[K+].[CH3:22][O:23][CH2:24]Cl>CN(C)C=O>[F:17][C:8]1[C:7]([O:6][CH2:22][O:23][CH3:24])=[CH:12][C:11]([F:13])=[CH:10][C:9]=1[CH2:14][C:15]#[N:16]

Participants

5

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 522689Potassium FluorideHCID 66890598(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}-2,5-difluorophenyl)acetonitrile

Product 1

HCID 66889518HCID 66889518, compoundYield 95.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}-2,5-difluorophenyl) acetonitrile (0.353 g, 1.25 mmol) was dissolved in dimethylformamide (3 mL) and potassium fluoride (0.145 g, 2.50 mmol) was added followed by chloromethyl methyl ether (0.117 mL, 1.54 mmol). The mixture was stirred at room temperature for 0.2 h and then 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 oil which was purified by column chromatography (ethyl acetate-hexanes 1:6) to afford (2,5-difluoro-3-{[(methyloxy)methyl]oxy}phenyl)acetonitrile as a light brown solid (0.253 g, 1.19 mmol, 95% yield). 1H NMR (400 MHz, CDCl3): 7.05-6.93 (m, 1H), 6.87-6.77 (m, 1H), 5.22 (s, 2H), 3.76 (s, 2H), 3.51 (s, 3H); GCMS for C10H9NO2: 213 (M+).

Workup

  1. customwas 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 oil which
  8. customwas purified by column chromatography (ethyl acetate-hexanes 1:6)

Sources & evidence

ORD record
ord-2703fba42c684f6687394e76404b68dc
Source dataset
uspto-grants-2011_01
Patent number
US07872014B2

Reaction notes

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