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

HRID 2415406Notes

Reaction equation

HRID 2415406 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:12]([O:19][C:20](=[O:34])[C@H:21]([CH2:23][C:24](OCC1C=CC=CC=1)=[O:25])[NH2:22])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.C([Mg]Cl)(C)(C)C.C(Cl)Cl>C(OCC)C>[CH2:12]([O:19][C:20]([C@H:21]1[NH:22][C:24](=[O:25])[CH2:23]1)=[O:34])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 2808531L-Aspartic acid, 1,4-bis(phenylmethyl) ester, 4-methylbenzenesulfonate (1:1)HCID 178418310HCID 178418310, compound

Product 1

HCID 717310Benzyl (2S)-4-oxoazetidine-2-carboxylateYield 57.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

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

Workup

  1. custom1 was synthesized
  2. customto achieve higher yields of 1
  3. customThe substrate in the flask was dried under high vacuum for 2 h
  4. additionfollowed by addition of TMSCI (6.588 mL, 0.052 mol)
  5. temperatureThe solution was slowly warmed to room temperature
  6. temperatureThe solution was then cooled again to 0° C.
  7. waitThe solution was kept at 0° C. for 2 h
  8. temperatureslowly warmed to room temperature
  9. washThe organic phase was washed with 1 N HCl (2×400 mL), saturated NaHCO3 (2×400 mL) and brine (2×400 mL)
  10. dry with materialThe organic phase was dried over MgSO4
  11. customAfter the solvent was removed
  12. customa yellow solid was obtained
  13. customThe solid was purified by crystallization from CH3OH

Sources & evidence

ORD record
ord-42dc7fbdaaa749b692d11652c936626c
Source dataset
uspto-grants-2004_11
Patent number
US06818732B2

Reaction notes

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