Sulfuric Acid → 5-Bromo-2-methyl-benzoic acid tert-butyl ester

HRID 1661574Notes

Reaction equation

HRID 1661574 reaction equation
S([O-])([O-])(=O)=O.[Mg+2].OS(O)(=O)=O.[Br:12][C:13]1[CH:14]=[CH:15][C:16]([CH3:22])=[C:17]([CH:21]=1)[C:18]([OH:20])=[O:19].[C:23](O)([CH3:26])([CH3:25])[CH3:24].C(=O)(O)[O-].[Na+]>ClCCl>[C:23]([O:19][C:18](=[O:20])[C:17]1[CH:21]=[C:13]([Br:12])[CH:14]=[CH:15][C:16]=1[CH3:22])([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 6386tert-ButanolHCID 24083Sulfuric acid magnesium salt (1:1)HCID 3460045-Bromo-2-methylbenzoic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 582156335-Bromo-2-methyl-benzoic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of anhydrous magnesium sulfate (4.5 g, 37.28 mmol) in dichloromethane (37 mL) is added concentrated H2SO4 (516 μl, 9.302 mmol) and the mixture is stirred vigorously for 15 min. 5-Bromo-2-methyl-benzoic acid (2 g, 9.302 mmol) is added, followed by t-butanol (4.39 mL, 46.51 mmol). The flask is capped tightly and stirred at room temperature for 24 h. After adding saturated sodium bicarbonate, the resulting solution is extracted with ethyl acetate. The organic layer is washed with a saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 3:7) to furnish 5-bromo-2-methyl-benzoic acid tert-butyl ester. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.59 (s, 9H), 2.51 (s, 3H), 7.08 (d, J=8.1 Hz, 1H), 7.46 (dd, J=8.3, 2.3 Hz, 1H), 7.92 (d, J=2.3 Hz, 1H)

Workup

  1. customThe flask is capped tightly
  2. stirringstirred at room temperature for 24 h
  3. extractionthe resulting solution is extracted with ethyl acetate
  4. washThe organic layer is washed with a saturated sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 3:7)

Sources & evidence

ORD record
ord-6593353e3cb146f58dc2eb2b263241bd
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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