Chemical Properties
WHITE TO VERY SLIGHTLY YELLOW CRYSTALLINE POWDER
Synthesis
The general procedure for the synthesis of trimethylacetamide from pivalic acid is as follows: to a 10 mL THF colorless solution containing 75 mg (0.50 mmol) of 3-phenylpropionic acid 1a at 0 °C, 67 μL (0.70 mmol, 1.4 eq.) of ethyl chloroformate and 209 μL (1.5 mmol, 3.0 eq.) of triethylamine were added sequentially. The reaction mixture was stirred at 0 °C for 30 min before adding 0.75 mL of 1.0 M NH4Cl aqueous solution (0.75 mmol, 1.5 equiv). Stirring was continued at 0 °C for 30 min, followed by the addition of 5 mL of water. The reaction mixture was extracted with 30 mL of ethyl acetate and the aqueous layer was then extracted with 20 mL of ethyl acetate. The organic layers were combined, washed with 5 mL of brine and dried with anhydrous magnesium sulfate. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate) to give 72 mg (96% yield) of 3-phenylpropionamide 2a. Synthesis of trimethylacetamide 2d: 44 mg (87% yield) of a colorless solid was obtained; melting point: 105-108 °C; 1H NMR (400 MHz, CDCl3): δ1.23 (s, 9H, CH3*3), δ1.21 (br, 1H, 1H). 5.21 (br, 1H, NHA), 5.59 (br, 1H, NHB); 13C NMR (100MHz, CDCl3): δ 27.7,38.7,181.6; IR (KBr, vmax/cm-1): 3398 (CONH), 3205 (CONH), 2960 (CH3), 1653 (CON), 1653 (CON). 1624 (CON); HRMS (ESI-TOF): calculated value C5H11NONa(M+Na)+: 124.0733, measured value: 124.0723.
References
[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2008, vol. 47, # 2, p. 315 - 318
[2] Chemistry Letters, 2008, vol. 37, # 12, p. 1191 - 1192
[3] Synthesis, 2003, # 2, p. 272 - 276
[4] Tetrahedron Asymmetry, 2017, vol. 28, # 12, p. 1690 - 1699
[5] Tetrahedron Letters, 2000, vol. 41, # 50, p. 9809 - 9813
