Chloromethyl Methyl Ether → HCID 44469521, compound

HRID 2382944Notes

Reaction equation

HRID 2382944 reaction equation
[Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]3[CH:12]=[N:13][N:14]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[C:15]=3[CH:16]=[CH:17][CH:18]=2)=[O:9])=[C:4]([Cl:28])[CH:3]=1.[H-].[Na+].[CH3:31][O:32][CH2:33]Cl>CN(C=O)C.O.C(OCC)C>[Br:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][N:7]([CH2:31][O:32][CH3:33])[C:8]([C:10]2[C:11]3[CH:12]=[N:13][N:14]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[C:15]=3[CH:16]=[CH:17][CH:18]=2)=[O:9])=[C:4]([Cl:28])[CH:3]=1

Participants

7

Reactant 3

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 44469517HCID 44469517, compound

Product 1

HCID 44469521HCID 44469521, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a room temperature solution of 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-bromo-2-chloro-benzylamide (1.5 g, 3.3 mmol) in DMF (30 mL) was added a 60% dispersion of sodium hydride in mineral oil (145 mg, 3.60 mmol). After stirring for 10 minutes, chloromethyl methyl ether (0.28 mL, 3.6 mmol) was added. After 16 hours, the mixture was then diluted with water (30 mL) and extracted with ethyl acetate (3×20 mL). The extract was washed with saturated aqueous ammonium chloride (30 mL) followed by brine (30 mL) and dried over sodium sulfate. The residue was purified by silica gel chromatography eluting with a gradient of 0-70% ethyl acetate in hexanes. The fractions containing product were condensed in vacuo to provide a colorless oil. The oil was dissolved in diethyl ether (25 mL), causing the starting material to solidify from solution. Filtration gave the title compound as a white solid.

Workup

  1. waitAfter 16 hours
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. washThe extract was washed with saturated aqueous ammonium chloride (30 mL)
  4. dry with materialdried over sodium sulfate
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with a gradient of 0-70% ethyl acetate in hexanes
  7. additionThe fractions containing product
  8. customcondensed in vacuo
  9. customto provide a colorless oil
  10. filtrationFiltration

Sources & evidence

ORD record
ord-0d5f85b1def5426c9d68ee82427fa903
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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