ETHYL 4-IODOBUTYRATE

ETHYL 4-IODOBUTYRATE Property

Boiling point:

84-85 °C(Press: 4 Torr)

Density 

1.614±0.06 g/cm3(Predicted)

storage temp. 

2-8°C(protect from light)

Hazard and Precautionary Statements (GHS)

ETHYL 4-IODOBUTYRATE Chemical Properties,Usage,Production

Synthesis Reference(s)

Synthetic Communications, 11, p. 763, 1981 DOI: 10.1080/00397918108063655

Synthesis

The general procedure for the synthesis of ethyl 4-bromobutyrate from ethyl 4-bromobutyrate was as follows: in a 100 mL round-bottom flask, ethyl 4-bromobutyrate (6.0 mL, 40.2 mmol) was dissolved in 40 mL of acetone. Potassium iodide (13.35 g, 80.4 mmol, 2.0 eq.) was added, a reflux condenser was installed, and the reaction mixture was heated to reflux for 12 hours. After completion of the reaction, the solution was cooled to room temperature, filtered through a sintered glass funnel and the filtrate was concentrated under reduced pressure. The resulting yellow oil containing fine particles was dissolved in about 50 mL of a 1:1 hexane/ether solvent mixture and filtered through a neutral alumina column for decolorization. After rinsing with an additional 100 mL of mixed 1:1 hexane/ether solvent, the solution was concentrated to give 8.44 g (87% yield) of ethyl 4-iodobutyrate. The product was characterized by 1H NMR (300 MHz, CDCl3): δ 4.14 (q, J = 7.2 Hz, 2H), 3.24 (t, J = 6.8 Hz, 2H), 2.44 (t, J = 7.1 Hz, 2H), 2.13 (m, 2H), 1.26 (t, J = 7.2 Hz, 3H). Next, a 50 mL Schlenk flask was flame-dried under vacuum, cooled to 23°C, and then ethyl 4-iodobutyrate (8.4 g, 34.7 mmol) and cuprous(I) iodide (10 mg, 0.05 mmol) were added. After sealing with a lubricated, ground glass stopper, the flask was evacuated and refilled with argon. The glass stopper was replaced with a rubber septum and diethylzinc (14 mL, 137 mmol, 4 equiv) was added via syringe. The reaction mixture was heated at 40°C for 12 hours. Upon completion of the reaction, the excess diethylzinc and ethyl iodide were removed under reduced pressure for 2 hours into a methanol trap cooled to -78°C with dry ice and acetone. (Note: Traps cooled with liquid nitrogen are safer, as dry ice/acetone cooling may not be sufficient to fully trap the volatiles. Methanol is used to quench excess diethylzinc, but care should be taken when cleaning the trap as small amounts of diethylzinc may remain). Under argon protection, 5 mL of THF is added to the reaction vessel and heated at 40°C for 1 hour. The reaction vessel was then evacuated for 1 hour. This process was repeated twice. After cooling to 23°C, the resulting bis(4-ethoxy-4-oxobutyl)zinc is diluted with 15 mL of THF, and the solution can be used directly in subsequent symmetrization reactions.

References

[1] Synthetic Communications, 2009, vol. 39, # 1, p. 61 - 69
[2] Journal of Organic Chemistry, 2004, vol. 69, # 9, p. 3025 - 3035
[3] Advanced Synthesis and Catalysis, 2007, vol. 349, # 8-9, p. 1533 - 1536
[4] Journal of Organic Chemistry, 2007, vol. 72, # 18, p. 6816 - 6823
[5] Synthesis (Germany), 2018, vol. 50, # 22, p. 4343 - 4350