1-(tert-Butoxycarbonyl)-2-pyrrolidinone

Uses

N-Boc-2-pyrrolidinone is a useful synthetic intermediate. It can be used to prepare highly functionalized N-acyl-2-vinylpyrrolidines by a 4-component Ugi reaction (isocyanide, carbonyl compounds, primary amines, carboxylic acids). It can also be used to synthesize the naturally occurring Maillard flavors via catalytic SeO2 oxidation.

General Description

The kinetics of gas-phase elimination of 1-(tert-butoxycarbonyl)-2-pyrrolidinone has been investigated in a static system. The observed rate coefficient has been reported to be log k₁(s^-1) = (11.54 ± 0.29) -(140.8 ± 2.8)-kJmol^-1 (2.303RT)^-1.

Synthesis

To a solution of 2-pyrrolidone (10.0 g, 118 mmol) in acetonitrile (118 mL) was sequentially added triethylamine (19.6 mL, 141 mmol), 4-dimethylaminopyridine (7.18 g, 58.8 mmol) and di-tert-butyl dicarbonate (32.7 g). The reaction mixture was stirred to room temperature at 0 °C and continued to stir overnight. After completion of the reaction, the mixture was partitioned between ethyl acetate and water. The organic layer was separated and washed sequentially with 1N aqueous hydrochloric acid, 1N aqueous sodium hydroxide and saturated saline. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane: ethyl acetate = 1:1) to afford 1-(tert-butoxycarbonyl)-2-pyrrolidinone (21.0 g, 96%) as a light yellow oil.1H-NMR (CDCl3, Varian, 400 MHz): δ 1.53 (9H, s), 2.00 (2H, quintuple peak, J = 8.0 Hz), 2.52 (2H, triple peak, J = 8.0 Hz), 3.75 (2H, triple peak, J = 7.6 Hz).

References

[1] Tetrahedron Letters, 1995, vol. 36, # 49, p. 8949 - 8952
[2] Synlett, 2004, # 9, p. 1625 - 1627
[3] Journal of Organic Chemistry, 2008, vol. 73, # 4, p. 1608 - 1611
[4] Tetrahedron, 2008, vol. 64, # 51, p. 11568 - 11579
[5] Chemistry - A European Journal, 2010, vol. 16, # 24, p. 7256 - 7264