N-acylation of an amide using acryloyl chloride
SyntheticPage 91
DOI:
Submitted: August 17, 2001, published: August 17, 2001
Authors
Mala Mistry (m.mistry@sussex.ac.uk)
A contribution from
Chemicals
Acryloyl chloride (Acros)
Dichloromethane (distilled from calcium hydride)
N-Ethyldiisopropylamine (Lancaster)
Dichloromethane (distilled from calcium hydride)
N-Ethyldiisopropylamine (Lancaster)
Procedure
To a stirring solution of the acryloyl chloride (47 uL, 0.578 mmol, 1.1 eq.) and N-ethyldiisopropylamine (0.1 mL , 0.578 mmol, 1.1 eq.) in dichloromethane (3 mL), was added a solution of the chiral auxiliary (0.1 g, 0.526 mmol, 1 eq.) and
N-ethyldiisopropylamine (91 uL, 0.526 mmol, 1 eq.) in dichloromethane (5 mL) by cannula. The reaction was at room temperature and under nitrogen. The reaction mixture was stirred for 2 hours and quenched by adding saturated ammonium chloride solution(10 mL). Work up involved dilution with dichloromethane (10 mL) and the combined organic extracts were dried, filtered and the solvent removed to afford a yellow solid. A short column eluting with 10:1-0:1 PE:Et2O gave the required product as a white solid (128 mg, 100 %).
Author Comments
We have coupled various acid chlorides to the imidazolidinone using 2,6-Lutidine, however in this particular case we were obtaining particularly disappointing yields (< 50 %). This procedure is from the literature where the group coupled an acryloyl chloride to a thiazolidine which is very similar to our system. However instead of quenching with water, I modifyied the protcol slightly by quenching with sat. NH4Cl solution.
This method has been carried out at both low to high scales ranging from 10 mg to 500 mg of the imidazolidinone.
Data
1H NMR (300 MHz, CDCl3) 0.78 (3H, d, J 6.60, CCH3) 2.83 (3H, s, NCH3) 3.85-3.89 (1H, m, CHCH3) 5.32 (1H, d, J 8.53, CHPh) 5.72 (1H, d, J 8.41, CHCH2) 6.27 (1H, d, J 19.07, CHCH2) 7.11-7.48 (5H, m, CHar)7.63-7.72 (1H, dd, CHCH2)
Lead Reference
N.A. Porter, I.J. Rosentein, R.A. Breyer, J.D. Bruhnke, W. Wu, A.T. McPhail; J. Am. Chem. Soc, 1992, 114 7664-7676.
Keywords
Comments
a good conversion
By Dr.G.Bijukumar on September 21, 2004