Diisopropylethylamine → p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[3-(t-butyldiphenylsilyloxy)-azetidin-1-ylcarbonyl]-1,3-oxazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate

To a solution of 3-acetylthio-1-{4-[3-(t-butyldiphenylsilyloxy)-azetidin-1-ylcarbonyl]-1,3-oxazol-2-yl}azetidine (860 mg, 1.61 mmol) (obtained as described in Reference Example 74) in dimethylformamide (43 ml) was added hydrazine acetate (178 mg, 1.93 mmol) at room temperature under an atmosphere of nitrogen and the mixture was stirred for 1 hour. After checking the completion of the reaction, a solution of p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (957 mg, 1.61 mmol) in acetonitrile (48 ml) was added dropwise into the resulting mixture in an ice bath under an atmosphere of nitrogen, followed by the addition of diisopropylethylamine (1.12 ml, 6.44 mmol). The mixture was stirred overnight while gradually raising the temperature to room temperature. After checking the completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogencarbonate solution were added to the reaction mixture. The resulting mixture was shaken in a separatory funnel and the ethyl acetate layer was separated, washed with 10% sodium chloride solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate:methanol (95:5)) to afford p-nitrobenzyl (1R,5S,6S)-2-(1-{4-[3-(t-butyldiphenylsilyloxy)-azetidin-1-ylcarbonyl]-1,3-oxazol-2-yl}azetidin-3-yl)thio-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (1.20 g, yield 89%) as a pale yellow solid.

1. customthe completion of the reaction
2. stirringThe mixture was stirred overnight
3. additionwere added to the reaction mixture
4. stirringThe resulting mixture was shaken in a separatory funnel
5. customthe ethyl acetate layer was separated
6. washwashed with 10% sodium chloride solution and saturated aqueous sodium chloride solution
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by chromatography on a silica gel column (eluant: ethyl acetate→ethyl acetate:methanol (95:5))

ORD-Eintrag

ord-cedfe70c1a7b4bd19065b88e25e38f26

Quelldatensatz

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07001897B2