Hydrochloric Acid → 1-Bromo-2-fluoro-4-methyl-5-(2,2,2-trichloro-ethyl)-benzene

HRID 1022384Notes

Reaction equation

HRID 1022384 reaction equation
[C:1]([Cl:4])([Cl:3])=[CH2:2].N(OC(C)(C)C)=O.[Br:12][C:13]1[C:14]([F:21])=[CH:15][C:16]([CH3:20])=[C:17](N)[CH:18]=1.[ClH:22]>C(#N)C.[Cu](Cl)Cl>[Br:12][C:13]1[CH:18]=[C:17]([CH2:2][C:1]([Cl:22])([Cl:4])[Cl:3])[C:16]([CH3:20])=[CH:15][C:14]=1[F:21]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6366Vinylidene chlorideHCID 10906Tert-Butyl nitriteHCID 27827865-Bromo-4-fluoro-2-methylaniline

Product 1

HCID 596145891-Bromo-2-fluoro-4-methyl-5-(2,2,2-trichloro-ethyl)-benzene

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of vinylidene chloride (127 ml), tert-butyl nitrite (19 ml) and copper(II)chloride (18.4 g) in acetonitrile (150 ml) is added a solution of 5-bromo-4-fluoro-2-methyl-phenylamine (Bioorganic & Medicinal Chemistry Letters (2006), 16(2), 457-460) (21.5 g) in acetonitrile (100 ml) dropwise below 20° C. The reaction mixture is stirred at room temperature for 48 hours, poured on diluted HCl and extracted with tert-butyl methyl ether (3×). The combined organic layers are washed with brine, dried over sodium sulfate and concentrated. The residue is purified by chromatography on silica gel (ethyl acetate/cyclohexane 1:4). Yield: 29.20 g of 1-bromo-2-fluoro-4-methyl-5-(2,2,2-trichloro-ethyl)-benzene as an oil.

Workup

  1. extractionextracted with tert-butyl methyl ether (3×)
  2. washThe combined organic layers are washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is purified by chromatography on silica gel (ethyl acetate/cyclohexane 1:4)

Sources & evidence

ORD record
ord-e515b355808d4250a7969a257faf3de5
Source dataset
uspto-grants-2014_05
Patent number
US08722578B2

Reaction notes

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