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0 °C

To a solution of allyl (4R)-2-diazo-4-[(2R,3S)-3-{(1R)-1-hydroxyethyl}-4-oxoazetidin-2-yl]-3-oxopentanoate (621 mg) in ethyl acetate (10 ml) was added rhodium(II) octanoate (10 mg) under nitrogen atmosphere, which was heated under reflux for 30 minutes. The solvent was evaporated and the remaining ethyl acetate was removed as the acetonitrile (10 ml) azeotrope to give a residue, which was dissolved in acetonitrile (10 ml) and cooled to 0° C. under nitrogen atmosphere. To the solution were added diphenyl chlorophosphate (480 μl), N,N-diisopropyl-N-ethylamine (421 μl) and N,N-dimethylacetamide (5 ml), and the solution was stirred for 10 hours at 0° C. To the solution was added at 0° C. a reaction mixture of (2S,4S)-4-acetylthio-1-allyloxycarbonyl-2-(2-fluoropropyl)oxymethylpyrrolidine (790 mg) and 28% sodium methoxide (485 μl) in acetonitrile (5 ml) which reaction had been carried out at -20° C. for 15 minutes. The reaction mixture was allowed to warm at ambient temperature and stirred for 5 hours, which was poured into a mixture of ethyl acetate (50 ml) and water (20 ml). The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo to give a residue, which was chromatographed on silica gel (100 ml) eluting with a mixture of hexane and ethyl acetate (1:1-1:2 V/V) to give allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (300 mg).

1. temperaturewhich was heated
2. temperatureunder reflux for 30 minutes
3. customThe solvent was evaporated
4. customthe remaining ethyl acetate was removed as the acetonitrile (10 ml)
5. customto give a residue, which
6. additionTo the solution was added at 0° C.
7. waithad been carried out at -20° C. for 15 minutes
8. temperatureto warm at ambient temperature
9. stirringstirred for 5 hours
10. customThe organic layer was separated
11. washwashed with brine
12. dry with materialdried over magnesium sulfate
13. customevaporated in vacuo
14. customto give a residue, which
15. customwas chromatographed on silica gel (100 ml)
16. washeluting with a mixture of hexane and ethyl acetate (1:1-1:2 V/V)