Methyl 3-phenylpropionate → N-methoxy-N-methyl-3-phenylpropanamide

Participants

Reaction Steps

Following a procedure of Trost (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006)); to a slurry of N,O-dimethylhydroxylamine hydrochloride (4.91 g, 50.4 mmol, 2.1 eq.) in toluene (50 ml) at −10° C. was added AlMe3 (2 M in hexanes, 25.2 ml, 50.4 mmol, 2.1 eq.) dropwise. After addition, the mixture was allowed to warm to r.t. and stirred for 1 h. The mixture was cooled to −5° C. and a solution of methyl 3-phenylpropanoate 82 (3.94 g, 24.0 mmol, 1 eq.) in toluene (40 ml) was added dropwise. The reaction mixture was then allowed to warm slowly to r.t. and stirred for 3 h. The solution was cooled to 0° C. and quenched carefully by dropwise addition of HCl and the reaction mixture was extracted with EtOAc (4×70 ml). The combined organic phases were washed with brine (50 ml) before being dried (MgSO4), filtered and concentrated to give the crude product. This was purified by column chromatography on silica, eluting with petrol/EtOAc (80:20 to 75:25), giving the Weinreb amide 83 as a clear, colourless oil (4.45 g, 97%). Analytical data consistent with the literature (Trost, B. M. et al., J. Am. Chem. Soc. 128, 6745-6754 (2006); Murphy, J. A. et al., Org. Lett. 7, 1427-1429 (2005)).

Provenance & Evidence