tert-Butanol → tert-Butyl (4-bromothiophen-2-yl)carbamate

HRID 2108746Notes

Reaction equation

HRID 2108746 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](C(O)=O)[S:5][CH:6]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:17])C=CC=CC=1.C([N:29]([CH2:32]C)CC)C.[CH3:34][C:35]([OH:38])([CH3:37])[CH3:36]>CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([NH:29][C:32](=[O:17])[O:38][C:35]([CH3:37])([CH3:36])[CH3:34])[S:5][CH:6]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 6104094-Bromo-2-thiophenecarboxylic Acid

Product 1

HCID 56763855tert-Butyl (4-bromothiophen-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-Bromothiophene-2-carboxylic acid (1.75 g, 8.5 mmol) was dissolved in 40 mL of t-BuOH. To this solution diphenylphosphoryl azide (2.8 g, 10.2 mmol) and triethylamine (1.4 mL, 10.1 mmol) were added. The reaction mixture was heated to reflux for 5 hours, cooled room temperature, and diluted with EtOAc. The organic layer was washed with 10% citric acid, saturated sodium bicarbonate and brine, and concentrated to an oil, which was purified by column chromatography on silica (0 to 25% EtOAc/hexanes) to give the product, 1.3 g, 4.7 mmol, 55%. 1H NMR 500 MHz (CDCl3) 6.96 (1H, br s), 6.83 (1H, s), 6.43 (1H, s), 1.54 (9H, s).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 5 hours
  3. washThe organic layer was washed with 10% citric acid, saturated sodium bicarbonate and brine
  4. concentrationconcentrated to an oil, which
  5. customwas purified by column chromatography on silica (0 to 25% EtOAc/hexanes)
  6. customto give the product, 1.3 g, 4.7 mmol, 55%

Sources & evidence

ORD record
ord-0a3fa9dbad6f470d9c1c909f30fe8daa
Source dataset
uspto-grants-2009_04
Patent number
US07514448B2

Reaction notes

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