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

HRID 1719307Notes

Reaction equation

HRID 1719307 reaction equation
C([Li])CCC.[OH:6][C:7]([C@@H:10]1[C@@H:13]([CH2:14][CH:15]=[CH2:16])[N:12]([C:17](=[C:22]([CH3:24])[CH3:23])[C:18]([O:20][CH3:21])=[O:19])[C:11]1=[O:25])([CH3:9])[CH3:8].Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=1)=[O:28].C(O)(=O)C>O1CCCC1>[CH3:23][C:22]([CH3:24])=[C:17]([N:12]1[C@H:13]([CH2:14][CH:15]=[CH2:16])[C@@H:10]([C:7]([CH3:9])([O:6][C:27]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=2)=[O:28])[CH3:8])[C:11]1=[O:25])[C:18]([O:20][CH3:21])=[O:19]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 782054-Nitrobenzyl chloroformateHCID 22823199methyl 2-[(3S,4R)-3-(1-hydroxy-1-methylethyl)-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoateHCID 178418339Butyllithium

Product 1

HCID 56623914methyl 2-{(3S,4R)-3-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-2-oxo-4-allylazetidin-1-yl}-3-methylbut-2-enoateYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

A solution of n-butyl lithium (0.42 ml of 1.55M solution in hexane) was added to a solution of methyl 2-[(3S,4R)-3-(1-hydroxy-1-methylethyl)-2-oxo-4-allylazetidin-1-yl]-3-methylbut-2-enoate (150 mg) in tetrahydrofuran (3 ml) during 3 minutes at -70° C. and the mixture was stirred for 5 minutes at -70° C. A solution of p-nitrobenzyl chloroformate (161 mg) in tetrahydrofuran (1.6 ml) was added to the mixture during 5 minutes at -70° C. and the mixture was stirred for 15 minutes at -70° C. The mixture was allowed to warm to 0° C. during 30 minutes and stirred for 2 hours at 0° C. Acetic acid (0.037 ml) was added to the mixture at 0° C. and the mixture was evaporated in vacuo. The residue was dissolved in ethyl acetate (50 ml), and was washed with water (10 ml), 10% phosphoric acid (10 ml), phosphate buffer (pH 7.0) (10 ml×2), aqueous sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (10 g) eluting with a mixture of hexane and ethyl acetate (5:1-1:1) to give methyl 3-methyl-2-[(3S,4R)-3-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-2-oxo-4-allylazetidin-1-yl]but-2-enoate (135 mg) as an oil.

Workup

  1. stirringthe mixture was stirred for 15 minutes at -70° C
  2. temperatureto warm to 0° C. during 30 minutes
  3. stirringstirred for 2 hours at 0° C
  4. customthe mixture was evaporated in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (50 ml)
  6. washwas washed with water (10 ml), 10% phosphoric acid (10 ml), phosphate buffer (pH 7.0) (10 ml×2), aqueous sodium bicarbonate and brine
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on silica gel (10 g)
  10. washeluting with a mixture of hexane and ethyl acetate (5:1-1:1)

Sources & evidence

ORD record
ord-83bf0ec56d2342c1909b7271bfe1847c
Source dataset
uspto-grants-1985_09
Patent number
US04539152

Reaction notes

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