Acetone → methyl 2-{(3R,4R)-3-isocyano-3-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-2-oxo-4-allylazetidin-1-yl}-3-methylbut-2-enoate

HRID 851416Notes

Reaction equation

HRID 851416 reaction equation
[N+:1]([C@@H:3]1[C@@H:6]([CH2:7][CH:8]=[CH2:9])[N:5]([C:10](=[C:15]([CH3:17])[CH3:16])[C:11]([O:13][CH3:14])=[O:12])[C:4]1=[O:18])#[C-:2].C([Li])CCC.[CH3:24][C:25]([CH3:27])=[O:26].Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=1)=[O:30]>O1CCCC1.C(O)(=O)C>[N+:1]([C@@:3]1([C:25]([CH3:27])([O:26][C:29]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=2)=[O:30])[CH3:24])[C@@H:6]([CH2:7][CH:8]=[CH2:9])[N:5]([C:10](=[C:15]([CH3:17])[CH3:16])[C:11]([O:13][CH3:14])=[O:12])[C:4]1=[O:18])#[C-:2]

Participants

7

Reactant 4

HCID 180AcetoneHCID 782054-Nitrobenzyl chloroformateHCID 54071546methyl 2-[(3R,4R)-3-isocyano-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoateHCID 178418339Butyllithium

Product 1

HCID 53687939methyl 2-{(3R,4R)-3-isocyano-3-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-2-oxo-4-allylazetidin-1-yl}-3-methylbut-2-enoate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of methyl 2-[(3R,4R)-3-isocyano-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoate (127.6 mg) in tetrahydrofuran (2.55 ml) was added dropwise a solution of n-butyl lithium (0.409 ml of 1.51 M solution in hexane) at -78° C. over a period of 3 minutes. After stirring for 15 minutes at -78° C., the reaction mixture was added dropwise with a solution of acetone (0.0459 ml) in tetrahydrofuran (0.459 ml) at -78° C. over a period of 3 minutes. After stirring for 25 minutes at -78° C., the reaction mixture was added dropwise with a solution of 4-nitrobenzyl chloroformate (124.1 mg) in tetrahydrofuran (1.24 ml) at -78° C. over a period of 3 minutes. The resulting solution was allowed to warm to 0° C. over a period of 40 minutes and added with acetic acid (0.0412 ml) at 0° C. The solvent was distilled off in vacuo at 0° C. and the residue was dissolved in ethyl acetate (30 ml) and washed with brine, aqueous sodium bicarbonate, brine and saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate extract was filtered and evaporated in vacuo. The residual oil (285.4 mg) was chromatographed on silica gel (5.7 g) eluting with a mixture of ethyl acetate and hexane (1:5→1:3) to give methyl 2-{(3R, 4R)-3-isocyano-3-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-2-oxo-4-allylazetidin-1-yl}-3-methylbut-2-enoate (211.2 mg) as an oil.

Workup

  1. stirringAfter stirring for 25 minutes at -78° C.
  2. temperatureto warm to 0° C. over a period of 40 minutes
  3. distillationThe solvent was distilled off in vacuo at 0° C.
  4. dissolutionthe residue was dissolved in ethyl acetate (30 ml)
  5. washwashed with brine, aqueous sodium bicarbonate, brine and saturated aqueous sodium chloride
  6. dry with materialAfter drying over magnesium sulfate
  7. extractionthe ethyl acetate extract
  8. filtrationwas filtered
  9. customevaporated in vacuo
  10. customThe residual oil (285.4 mg) was chromatographed on silica gel (5.7 g)
  11. washeluting with a mixture of ethyl acetate and hexane (1:5→1:3)

Sources & evidence

ORD record
ord-a73cc8f8074d4d6b88213195454f28d6
Source dataset
uspto-grants-1983_05
Patent number
US04383945

Reaction notes

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