Phosgene → (S)-N-[[3-[[(Phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]N-methyl-DL-alanine, phenylmethyl ester

温度

0 °C

A solution of phosgene in toluene (4.7 ml of a 20% solution, 9.36 mmol) was cooled to -25° C. under argon. While stirring, a solution (pre-cooled to 0° C.) of N-methyl-DL-alanine, benzyl ester (1.0 g, 5.2 mmol) and triethylamine (870 μl, 6.25 mmol) in dichloromethane (5 ml) was added over 5 minutes maintaining the temperature at -20° to -25° C. After stirring at -25° C. for 1 hour, solvent and excess phosgene were removed in vacuo. The residue was dissolved in dichloromethane (12 ml), cooled to 0° C. and then (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (1.15 g, 5.2 mmol), dimethylaminopyridine (63 mg, 0.52 mmol), and triethylamine (870 μl, 6.2 mmol) were added sequentially. Stirring was continued for 10 minutes at 0° C. and then overnight at room temperature. After refluxing for an additional 7 hours, the mixture was again stirred overnight at room temperature. The mixture was washed with water, dried (Na2SO4) and solvent was removed in vacuo. The resulting oil was chromatographed on silica gel eluting with a 4:6 ethyl acetate:hexane mixture. The desired product was obtained as an oil (580 mg).

1. temperaturemaintaining the temperature at -20° to -25° C
2. stirringAfter stirring at -25° C. for 1 hour
3. customsolvent and excess phosgene were removed in vacuo
4. dissolutionThe residue was dissolved in dichloromethane (12 ml)
5. stirringStirring
6. customovernight
7. customat room temperature
8. temperatureAfter refluxing for an additional 7 hours
9. waitthe mixture was again stirred overnight at room temperature
10. washThe mixture was washed with water
11. dry with materialdried (Na2SO4) and solvent
12. customwas removed in vacuo
13. customThe resulting oil was chromatographed on silica gel eluting with a 4:6 ethyl acetate

ORDレコード

ord-cba0cb31a43d4dd6a17e49c9769038e5

出典データセット

uspto-grants-1986_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04576749