N-acylation of an amide using acryloyl chloride ; 1-acryloyl-3,4-(S)-dimethyl-5-(R)-phenyl-imidazolidin-2-one
Submitted Aug 17, 2001, published Aug 17, 2001
Acryloyl chloride (Acros)
Dichloromethane (distilled from calcium hydride)
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 %).
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)
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: chiral auxiliary, imidazolidinone, acryloyl chloride, DIPEA, Hunigs Base, alkenes, 6-Lutidine, coupling, 91