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

HRID 2117592Notes

Reaction equation

HRID 2117592 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-3113bd47f3e64300984a7b62ca4f79f8
Source dataset
uspto-grants-2008_10
Patent number
US07442702B2

Reaction notes

Loading…