Dichloromethane → Benzyl (2S)-4-oxoazetidine-2-carboxylate

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Reaction Conditions

Reaction Steps

1 was synthesized according to a procedure similar to that reported by Salzmann.20 A modified procedure31 was adopted to achieve higher yields of 1. Commercially available L-aspartic acid dibenzyl ester p-toluenesulfonate salt (25 g 0.052 mol) was charged to a dry schlenk flask. The substrate in the flask was dried under high vacuum for 2 h. Dry CH2Cl2 (450 mL) was transferred to the flask under N2 and then the solution was cooled to 0° C. using an ice bath. Triethyl amine (15.8 mL, 0.1133 mol, 2.2 eq) was added and followed by addition of TMSCI (6.588 mL, 0.052 mol). The solution was slowly warmed to room temperature and stirred for an additional 12 h. The solution was then cooled again to 0° C. and tert-BuMgCl (77 mL of a 2.0 M solution in diethyl ether, 3.0 eq) was slowly added to the mixture. The solution was kept at 0° C. for 2 h and then slowly warmed to room temperature. The reaction was stopped 10 h later by addition of 200 mL wet CH2Cl2. The organic phase was washed with 1 N HCl (2×400 mL), saturated NaHCO3 (2×400 mL) and brine (2×400 mL). The organic phase was dried over MgSO4. After the solvent was removed, a yellow solid was obtained. The solid was purified by crystallization from CH3OH and then sublimation at 110° C. under high vacuum to give 1 as white crystals (6.1 g, 55%). FTIR (THF): 1779 cm−1 (νCO, lactam, s), 1747 cm−1 (νCO, ester, s). 1H NMR (CDCl3, 500 MHz) δ 7.25 (s, 5H, CH2C(O)NHCH(CO2CH2C6H5)), 6.0 (br, 1H, CH2C(O)NHCH(CO2CH2C6H5)), 5.15 (s, 2H, CH2C(O)NHCH(CO2CH2C6H5)), 4.24 (dd, 1H, CH2C(O)NHCH(CO2CH2C6H5)), 3.36 (ddd, 1H, CH2C(O)NHCH(CO2CH2C6H5), 3.15 (ddd, 1H, CH2C(O)NHCH(CO2CH2C6H5)). 13C NMR (CDCl3, 200 MHz) δ 171.0, 166.5, 135.1, 128.9, 128.7, 67.7, 47.5, 43.8. FTIR, 1H NMR and 13C NMR spectra of this compound were identical to literature data for 1.12

Provenance & Evidence