Sulfuric Acid → Tert-butyl 5-bromothiophene-2-carboxylate

HRID 2300552Notes

Reaction equation

HRID 2300552 reaction equation
[O-]S([O-])(=O)=O.[Mg+2].OS(O)(=O)=O.[Br:12][C:13]1[S:17][C:16]([C:18]([OH:20])=[O:19])=[CH:15][CH:14]=1.[C:21](O)([CH3:24])([CH3:23])[CH3:22]>C(Cl)Cl>[C:21]([O:19][C:18]([C:16]1[S:17][C:13]([Br:12])=[CH:14][CH:15]=1)=[O:20])([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 6386tert-ButanolHCID 24083Sulfuric acid magnesium salt (1:1)HCID 3491155-Bromothiophene-2-carboxylic acid

Product 1

HCID 10912335Tert-butyl 5-bromothiophene-2-carboxylateYield 94.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of anhydrous MgSO4 (11.60 g, 96.4 mmol) in 100 mL CH2Cl2 was added concentrated H2SO4 (1.45 mL, 24.1 mmol) and the mixture was stirred for 15 minutes followed by addition of 5-bromo-thiophene-2-carboxylic acid (5.0 g, 24.1 mmol). After stirring for 1 minute, tert-butanol (11.6 g, 20 mmol) was added and the reaction was stirred at room temperature for 16 h. The reaction was quenched with saturated NaHCO3. The layers were separated, the aqueous layer was extracted with CH2Cl2, and the combined organic layers were dried over MgSO4. The organic solution was concentrated to give a clear oil which was purified via medium pressure chromatography (3% EtOAc in hexanes) to afford the title compound of Step A (4.97 g). 1H NMR (400 MHz, CDCl3) δ 7.45 (d, 1H), 7.02 (d, 1H), 1.54 (s, 9H).

Workup

  1. stirringAfter stirring for 1 minute
  2. stirringthe reaction was stirred at room temperature for 16 h
  3. customThe reaction was quenched with saturated NaHCO3
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. concentrationThe organic solution was concentrated
  8. customto give a clear oil which
  9. customwas purified via medium pressure chromatography (3% EtOAc in hexanes)

Sources & evidence

ORD record
ord-43c74a9ef01b429eb80829c2b933afc0
Source dataset
uspto-grants-2002_12
Patent number
US06498172B1

Reaction notes

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