Dimethyl Ether → 2-(4-Oxoazetidin-2-yl)ethyl acetate
Reaction equation
ClS([N:5]=[C:6]=[O:7])(=O)=O.[C:8]([O:11][CH:12]=[CH:13][CH:14]=[CH2:15])(=[O:10])[CH3:9].COC>>[C:8]([O:11][CH:12]=[CH:13][CH:14]1[NH:5][C:6](=[O:7])[CH2:15]1)(=[O:10])[CH3:9].[C:8]([O:11][CH2:12][CH2:13][CH:14]1[NH:5][C:6](=[O:7])[CH2:15]1)(=[O:10])[CH3:9]Participants
Procedure
In words relative to the above diagram for the preparation of 1, the 4-(2-acetoxyvinyl)azetidine-2-one (3) is prepared by reacting chloro sulphonyl isocyanate and an acyloxybutadiene such as 1-acetoxybutadiene in a solvent such as anhydrous dimethyl ether at a temperature of from about -30° C. to 0° C. under a nitrogen atmosphere. The reaction intermediate 2 is converted to 3 by hydrolysis. The reduction of 3 to provide the 4-(2-acetoxyethyl)-2-azetidinone (4) is conducted by any convenient means such as hydrogenation in the presence of a catalyst such as platinum, palladium or oxides thereof under a hydrogen pressure of from 1 to 20 atmospheres in a solvent such as ethanol, ethylacetate, or the like at a temperature of from 0° to 25° C., for from 5 minutes to 1 hour. The 4-(2-hydroxyethyl)-2-azetidinone species, 5, is obtained from 4 by hydrolysis. The 8-oxo- 2,2-dimethyl-3-oxa-1-azabicyclo[4.2.0]octane species, 6, is obtained on treatment of 5 with 2,2-dimethoxypropane in the presence of a catalyst such as boron trifluoride etherate in a solvent such as methylene chloride at a temperature of from 0° to 40° C. for from 1 to 40 minutes. The azide intermediate 7 is prepared by treating 6 in a solvent such as tetrahydrofuran (THF), dimethoxyethane, dioxane, DMF or the like with a base such as lithium diisopropylamide, butyl lithium, phenyl lithium or the like at a temperature of from -25° to -78° C. for from one to three hours; whereupon an azide reagent such as tosylazide is introduced; after 1 to 3 hours at -35° to -50° C. the mixture is treated with a disproportionating agent such as trimethylchlorosilane to provide the azide 7 which may be isolated. The amino intermediate 8 is prepared by reducing 7 in a solvent such as ethylacetate, ethanol, dioxane, methanol or the like in the presence of a hydrogenation catalyst such as Pd on carbon, PtO2, Pd/CaCO3, or the like and hydrogen (4 to 50 atmospheres) for from 12 to 48 hours at a temperature of from 20° to 30° C. The N-acyl intermediate 8a is obtained from 8 on treatment in a solvent such as CH2Cl2, ether, chloroform or the like with the acid chloride of choice calculated to provide the acyl radical R1 at a temperature of from -25° to 0° C. for from 2 to 15 hours. Species 9 is obtained from 8a by acid hydrolysis.
Workup
- customIn words relative to the above diagram for the preparation of 1
- customof from about -30° C. to 0° C.
Sources & evidence
- ORD record
- ord-d0d6e665ad1e401281d1bfe0f5baf166
- Source dataset
- uspto-grants-1980_08
- Patent number
- US04218459
Reaction notes
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