Acetic Acid → Methyl 4-bromo-3-methylthiophene-2-carboxylate

HRID 1465948Notes

Reaction equation

HRID 1465948 reaction equation
C[Si](C=[N+]=[N-])(C)C.[CH3:8]COCC.[Br:13][C:14]1[C:15]([CH3:22])=[C:16]([C:19]([OH:21])=[O:20])[S:17][CH:18]=1.C(O)(=O)C>CO.O1CCCC1>[CH3:8][O:20][C:19]([C:16]1[S:17][CH:18]=[C:14]([Br:13])[C:15]=1[CH3:22])=[O:21]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3283Diethyl EtherHCID 167693Trimethylsilyldiazomethane2×HCID 27570734-Bromo-3-methylthiophenecarboxylic acid

Product 1

HCID 59212115Methyl 4-bromo-3-methylthiophene-2-carboxylateYield 92.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The (trimethylsilyl)diazomethane solution in ether (2.0 M, 41.2 mL, 82.3 mmol) was added dropwise to a solution of 4-bromo-3-methyl-thiophene-2-carboxylic acid (13.0 g, 58.8 mmol, purchased from Oakwood Products) in methanol (50 mL) and tetrahydrofuran (50 mL) at ambient temperature. After the reaction mixture was stirred at ambient temperature for 30 min, acetic acid was added to decompose the excess (trimethylsilyl)diazomethane until the yellow color disappeared. Most of the solvent was evaporated and ethyl acetate was added. The organic solution was washed with saturated sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes to produce 12.8 g of a white solid. 1H NMR (CDCl3, 200 MHz): δ=7.40 (s, 1H), 3.87 (s, 3H), and 2.54 (s, 3H).

Workup

  1. customMost of the solvent was evaporated
  2. additionethyl acetate was added
  3. washThe organic solution was washed with saturated sodium bicarbonate solution and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography
  7. washeluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-11931a0ecc194d58ad485c2271dae191
Source dataset
uspto-grants-2015_04
Patent number
US09000006B2

Reaction notes

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