Methyl chloroformate → HCID 70019009, compound

Temperature

0 °C

Methyl chloroformate (29 /ml, 0.37 mol) was added dropwise to a cooled solution (0° C.) of (3R,4S)-4-tert-butoxycarbonylamino-3-hydroxycyclopent-1-enecarboxylic acid (83 g, 0.34 mol) and triethylamine (52 ml, 0.37 mol) in methanol (600 ml). The reaction was stirred for 1 h at 0° C. and then allowed to warm to room temperature. After stirring for 14 h, it was apparent that the reaction was incomplete. After cooling to 0° C., triethylamine (30 ml, 0.22 mol) was added, and then methyl chloroformate (15 ml, 0.19 mol) was added dropwise. The reaction was complete after a further 2 h. The reaction mixture was concentrated under vacuum and the residue redissolved in dichloromethane (400 ml). The organic solution was washed sequentially with 1M potassium hydrogen sulfate (aq) (2×200 ml), saturated hydrogen carbonate (2×200 ml) and brine (200 ml) before drying over magnesium sulfate. Following filtration, the solvent was removed to yield an orange oil which was redissolved in methanol (300 ml) and cooled to 5° C. Sodium methoxide (0.25 ml, 25% wt solution in methanol, 3 mol %) was then added and the reaction mixture cooled and stirred for 4 h. The reaction was quenched with glacial acetic acid and concentrated under vacuum, and the residue was redissolved in dichlormethane (300 ml). The organic solution was washed with saturated sodium hydrogen carbonate (100 ml) then brine (100 ml) and dried over magnesium sulfate. Following filtration, the solvent was removed under vacuum to yield the title compound as an orange oil (76 g, 87%).

1. temperatureto warm to room temperature
2. stirringAfter stirring for 14 h
3. temperatureAfter cooling to 0° C.
4. waitThe reaction was complete after a further 2 h
5. concentrationThe reaction mixture was concentrated under vacuum
6. dissolutionthe residue redissolved in dichloromethane (400 ml)
7. washThe organic solution was washed sequentially with 1M potassium hydrogen sulfate (aq) (2×200 ml), saturated hydrogen carbonate (2×200 ml) and brine (200 ml)
8. dry with materialbefore drying over magnesium sulfate
9. filtrationfiltration
10. customthe solvent was removed
11. customto yield an orange oil which
12. temperaturecooled to 5° C
13. temperaturethe reaction mixture cooled
14. stirringstirred for 4 h
15. customThe reaction was quenched with glacial acetic acid
16. concentrationconcentrated under vacuum
17. dissolutionthe residue was redissolved in dichlormethane (300 ml)
18. washThe organic solution was washed with saturated sodium hydrogen carbonate (100 ml)
19. dry with materialbrine (100 ml) and dried over magnesium sulfate
20. filtrationfiltration
21. customthe solvent was removed under vacuum

ORD record

ord-84c47498cc644de5973a685b89d25e09

Source dataset

uspto-grants-2003_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06593489B1