Ethyl chloroformate → Ethyl 3-(1-tert-butoxycarbonylaminocyclopropyl)propiolate

Temperatur

-55 °C

Under a nitrogen atmosphere, chloromethyltrimethylphosphonium chloride (5.156 g, 14.85 mmol) was suspended in anhydrous tetrahydrofuran (30 ml) to which, after cooling to −55° C., was subsequently added dropwise a 1.68 M n-butyl lithium n-hexane solution (8.87 ml, 14.90 mmol) over a period of 5 minutes. The reaction suspension was stirred for 30 minutes in an ice bath and for 3 hours at room temperature and then cooled to −55° C. To the reaction suspension was added dropwise an anhydrous tetrahydrofuran (10 ml) solution of 1-tert-butoxycarbonylaminocyclopropane carbaldehyde (2.498 g, 13.50 mmol) over a period of 10 minutes, subsequently stirring the mixture for 1 hour at −50° C. and then for 30 minutes in an ice bath. The reaction suspension was cooled to −78° C., an n-hexane solution of 1.68 M an n-butyl lithium (17.68 ml, 29.70 mmol) was added dropwise thereto over a period of 10 minutes and then the mixture was stirred at −78° C. for 20 minutes. Ethyl chloroformate (1.61 ml, 16.88 mmol) was added dropwise to the reaction suspension which was subsequently stirred for 1.5 hours at −78° C. and then for 1 hour in an ice bath. While cooling in an ice bath, the reaction suspension was mixed-with saturated brine (30 ml), the organic layer was separated and the aqueous layer was extracted with diethyl ether (30 ml×2). The organic layers were combined, washed with saturated brine (30 ml) and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting residue was applied to a flash silica gel chromatography column and eluted with an eluant of n-hexane:ethyl acetate=5:1, to-thereby obtain 2.178 g (63.9%) of the title compound as a colorless oil.

1. temperaturecooled to −55° C
2. stirringsubsequently stirring the mixture for 1 hour at −50° C.
3. waitfor 30 minutes in an ice bath
4. temperatureThe reaction suspension was cooled to −78° C.
5. waitover a period of 10 minutes
6. stirringthe mixture was stirred at −78° C. for 20 minutes
7. stirringwas subsequently stirred for 1.5 hours at −78° C.
8. waitfor 1 hour in an ice bath
9. temperatureWhile cooling in an ice bath
10. customthe organic layer was separated
11. extractionthe aqueous layer was extracted with diethyl ether (30 ml×2)
12. washwashed with saturated brine (30 ml)
13. dry with materialdried over anhydrous magnesium sulfate
14. filtrationAfter filtration
15. concentrationthe filtrate was concentrated under reduced pressure
16. washeluted with an eluant of n-hexane

ORD-Eintrag

ord-812e63109fe445ceb5faaab2b9125001

Quelldatensatz

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06184388B2