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TCI Practical Example: Synthesis of a Carbamate Using DPPA

We are proud to present the synthesis of the carbamate via the Curtius rearrangement using thiazole-4-carboxylic acid, DPPA and tert-butyl alcohol.

Used Chemicals

• Diphenylphosphoryl Azide (= DPPA) [D1672]
• Trimethylamine [T0424]
• tert-Butyl Alcohol [B0706]
• Thiazole-4-carboxylic Acid [T2494]

Procedure

DPPA (0.92 mL, 4.26 mmol, 1.1 equiv.) was added to a solution of thiazole-4-carboxylic acid (500 mg, 3.87 mmmol) and triethylamine (0.59 mL, 4.26 mmol, 1.1 equiv.) in tert-butyl alcohol (2 mL) at 0 °C and the solution was stirred for 30 minutes. Then, the reaction mixture was heated to 90 °C and stirred for 21 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by column chromatography (ethyl acetate:hexane = 0:1 - 1:1 on silica gel) to give tert-butyl N-thiazol-4-ylcarbamate as a white solid (591 mg, 76% yield).

Experimenter's Comments

The reaction mixture was monitored by HPLC.
TLC analysis of the target product showed Rf = 0.4 (ethyl acetate:hexane = 1:4).

Analytical Data

tert-Butyl N-Thiazol-4-ylcarbamate

¹H NMR (270 MHz, CDCl₃); δ 8.58 (d, J = 2.2 Hz, 1H), 8.06 (brs, 1H), 7.29 (brs, 1H), 1.51 (s, 9H).

Lead Reference

• Novel Syntheses of Variably Substituted Pyrrolo[2,3-d]thiazoles
  • H. Koolman, T. Heinrich, M. Reggelin, Synthesis 2010, 18, 3152.