Methacryloyl chloride → 1-(2-Methylacryloyl)-L-proline

Participants

Reaction Steps

A mechanically stirred mixture of L-proline (42.0 grams, g), NaHCO3 (148 g), H2O (680 milliliters, ml) and diethyl ether (280 ml) was maintained in an ambient temperature bath at pH 10.5-10.7 (adjusted by the addition of concentrated aqueous NaOH), then treated portionwise over 20 minutes with a solution of redistilled methacryloyl chloride (40 ml) in diethyl ether (20 ml). Additional concentrated aqueous NaOH was added as needed to keep the pH at 10.5-10.7. Upon addition of all of the methacryloyl chloride (and pH stabilization), the mixture was stirred for 20 minutes at ambient temperature. The resulting immiscible phases were separated and the aqueous phase was extracted with two 250 ml portions of diethyl ether. The combined organic extracts were washed with H2O (50 ml), and the aqueous extract was added to the aqueous phase which phase was then acidified to pH 1 with concentrated aqueous HCl and then extracted with four 250 ml portions of ethyl acetate. The combined ethyl acetate extracts were washed with about 100 ml of brine (saturated aqueous sodium chloride solution) and then dried over Na2SO4. The resulting solution was filtered and concentrated in vacuo to about 230 ml and then heated to boiling, diluted with hexane (80 ml) and allowed to cool. Upon cooling, the desired N-methacryloyl-L-proline spontaneously crystallized as chunky white prisms (51.3 g). The concentrated mother liquor yielded a second crop of crystals (4.26 g) when crystallized as described above. A portion of the first crop was recrystallized twice from ethyl acetate to give an analytical sample, m.p. 102°-104.5° C., having the following spectral characteristics:

Provenance & Evidence