1,4-Dibromobenzene → HCID 19043746, compound

HRID 2397049Notes

Reaction equation

HRID 2397049 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1.CON(C)[C:17](=[O:31])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][Si](C)(C)C)=[C:21]([F:30])[CH:20]=1>C1COCC1>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([C:17](=[O:31])[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[C:21]([F:30])[CH:20]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 78041,4-DibromobenzeneHCID 19043704HCID 19043704, compoundHCID 178418339Butyllithium

Product 1

HCID 19043746HCID 19043746, compoundYield 84.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 45 ml of n-butyllithium (1.6M in hexane) is added dropwise to a suspension, cooled to -78° C., of 18.2 g of 1,4-dibromobenzene in 140 ml of THF. Then, 10 g of N-methoxy-N-methyl-2-(3-fluoro-4-trimethylsilanyloxy-phenyl)-acetamide (paragraph Bb)) in 35 ml of THF are added dropwise at -78° C. The reaction mixture is stirred at -78° C. for 2 hours, then left to stand at room temperature for 1 hour while stirring. After dilution with ethyl acetate, the mixture is washed with 10% aqueous KHSO4 solution, saturated NaHCO3 solution and 10% aqueous NaCl solution. After extraction with ethyl acetate, the organic phases are dried and concentrated. Then, the silyl group is cleaved with 105 ml of THF, 11 ml of H2O and 5 drops of 1N HCl. Concentration, dissolution in methylene chloride, drying and column chromatography over silica gel with methylene chloride/0.5% methanol as the eluent, give 9.2 g of 1-(4-bromo-phenyl)-2-(3-fluoro-4-hydroxyphenyl)-ethanone. MS: m/e 308 (M+, 1 Br).

Workup

  1. waitleft
  2. waitto stand at room temperature for 1 hour
  3. stirringwhile stirring
  4. washAfter dilution with ethyl acetate, the mixture is washed with 10% aqueous KHSO4 solution, saturated NaHCO3 solution and 10% aqueous NaCl solution
  5. extractionAfter extraction with ethyl acetate
  6. customthe organic phases are dried
  7. concentrationconcentrated
  8. concentrationConcentration, dissolution in methylene chloride
  9. customdrying

Sources & evidence

ORD record
ord-2b45ab50ef8b4d1db869e0302748fbcd
Source dataset
uspto-grants-1996_02
Patent number
US05495048

Reaction notes

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