Hydrochloric Acid → 1-Methoxycarbonyl-1-(4-methylthio-2-oxoazetidin-1-yl)-3-phenyl-propan-2-one

Participants

Reaction Conditions

Reaction Steps

A solution of lithium 2,2,6,6-tetramethylpiperidide was prepared by adding butyl-lithium (2.0 ml of a 1.64 M solution in hexane) to a solution of 2,2,6,6-tetramethylpiperidine (0.45 g) in dry tetrahydrofuran (10 ml) at -70° C. under a nitrogen atmosphere. After 3 minutes a solution of methyl (4-methylthio-2-oxoazetidin-1-yl)acetate (0.346 g) in dry tetrahydrofuran (4 ml) was added quickly and the mixture stirred for 5 minutes at -70° C. A solution of phenylacetyl chloride (0.219 g) in dry tetrahydrofuran (4 ml) was then added quickly and the reaction allowed to proceed for 30 minutes at -70° C. and then 30 minutes during which time it warmed to 20° C. The mixture was acidifed with N hydrochloric acid at 0°-10° C. and extracted with ethyl acetate (3×50 ml). These extracts were combined, washed with water, dried (MgSO4) and evaporated. The residue (0.709 g) was chromatographed on silica gel eluting with 25% ethyl acetate in petrol-ether which provided the desired azetidinone (0.15 g, 37%) as a colourless gum which was a mixture of enolic isomers. νmax (CHCl3): 3500, 1760 (b), 1655, 1605, 1440, 1400, 1355, 1260 cm-1 ; δ(CDCl3): 2.00 and 2.06 (2s, 3H, SCH3); 2.7-3.6 (m, AB of ABX, 2H, CH2CH); 3.58, 4.09 (main peaks of ABq, J=17 Hz, CH2Ph); 3.69, 3.76 (2s, 3H, CO2CH3); 4.8 (m, 1H, CH) and 7.37 (s, 5H, Ph-H) ppm. If Lithium bis (trimethylsilyl) amide is used as the base in this example the yield of keto ester rises to 90%.

Provenance & Evidence