Hydrochloric Acid → 2-Bromo-5-(4-fluorobenzyl)thiophene

HRID 52192

Reaction equation

HRID 52192 reaction equation
[Li+].CC([N-]C(C)C)C.[Br:9][C:10]1[S:11][CH:12]=[CH:13][CH:14]=1.[F:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]Br)=[CH:18][CH:17]=1.Cl>C1COCC1>[Br:9][C:10]1[S:11][C:12]([CH2:20][C:19]2[CH:22]=[CH:23][C:16]([F:15])=[CH:17][CH:18]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 138512-BromothiopheneHCID 680214-Fluorobenzyl bromideHCID 2724682Lithium diisopropylamide

Product 1

HCID 105400132-Bromo-5-(4-fluorobenzyl)thiopheneYield 45.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a -78° C. solution of LDA (19.3 mmol) in THF was added 2-bromothiophene (3.00 g, 18.4 mmol) and the reaction mixture was stirred for 15 min. A solution of 4-fluorobenzyl bromide (3.65 g, 19.3 mmol) in THF (1 mL) was added dropwise and the reaction mixture was warmed slowly to ambient temperature and stirred for 70 hours. The reaction mixture was poured into 0.5N aqueous HCl and extracted twice with ether. The combined organic layers were washed with saturated aqueous NaHCO3 (2×) and brine, dried over MgSO4, filtered, and concentrated in vacuo. Chromatography on silica gel (hexanes, then 3% ether/hexanes) gave 2-bromo-5-(4-fluorophenylmethyl)thiophene (2.25 g, 45%).

Workup

  1. stirringstirred for 70 hours
  2. extractionextracted twice with ether
  3. washThe combined organic layers were washed with saturated aqueous NaHCO3 (2×) and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-68dedbc32e1846dabccd5c35808bec20
Source dataset
uspto-grants-1997_04
Patent number
US05616596

Linked notes

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