Chloromethyl Methyl Ether → HCID 131736021, compound

HRID 1049509Notes

Reaction equation

HRID 1049509 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[C:11]([OH:27])=[CH:12][C:13]([O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])=[CH:14][CH:15]=1.C(N(CC)C(C)C)(C)C.[CH3:37][O:38][CH2:39]Cl.[Cl-].[NH4+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][Si:17]([CH:21]([CH3:23])[CH3:22])([CH:24]([CH3:26])[CH3:25])[CH:18]([CH3:20])[CH3:19])=[CH:12][C:11]=1[O:27][CH2:37][O:38][CH3:39]

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 131736006HCID 131736006, compound

Product 1

HCID 131736021HCID 131736021, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2′-fluoro-5′-methoxy-4-((triisopropylsilyl)oxy)biphenyl-2-ol (4.01 g) and N,N-diisopropylethylamine (5.4 mL) in DMF (30 mL) was added chloromethyl methyl ether (1.5 mL), and the mixture was stirred at room temperature for 3 hr. The mixture was further stirred at 50° C. for 1 hr, and saturated aqueous ammonium chloride solution was added to the reaction mixture. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was dissolved in DMF (30 mL), and N,N-diisopropylethylamine (2.7 mL) and chloromethyl methyl ether (1.0 mL) were added. The reaction mixture was stirred at room temperature for 2 hr, and saturated aqueous ammonium chloride solution was added. The reaction mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (3.50 g) as a colorless oil.

Workup

  1. stirringThe mixture was further stirred at 50° C. for 1 hr
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionthe residue was dissolved in DMF (30 mL)
  7. additionN,N-diisopropylethylamine (2.7 mL) and chloromethyl methyl ether (1.0 mL) were added
  8. stirringThe reaction mixture was stirred at room temperature for 2 hr
  9. additionsaturated aqueous ammonium chloride solution was added
  10. extractionThe reaction mixture was extracted with ethyl acetate
  11. washthe extract was washed with saturated brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9fd1e3d3b35741fcae24e71352354faa
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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