Reaktion #2490072

Reaktionsgleichung

triethylamine

citric acid

Methyl-cyclopropanecarboxylic acid

oxalyl chloride

(1S,4S)-3-oxo-2-oxa-5-azonia-bicyclo[2.2.1]heptane methanesulfonate

→

title compound

Ausbeute 86.1%

(1S,4S)-5-(1-Methyl-cyclopropanecarbonyl)-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one

Ausbeute 86.1%

Lösungsmittel

water

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm
2. 2
   TemperaturThe resulting suspension was cooled to 2° C.
3. 3
   workup.STIRRINGAfter stirring for 70 min at room temperature
4. 4
   SonstigeAfter separation of the phases
5. 5
   Extraktionthe aqueous phase was extracted with dichloromethane (300 mL)
6. 6
   WaschenThe combined organic extracts were washed with water (400 mL)
7. 7
   Einengenconcentrated in vacuo to a volume of ca. 500 mL
8. 8
   workup.ADDITIONEthyl acetate (330 mL) was added
9. 9
   workup.DISTILLATIONthe residual dichloromethane was distilled off in vacuo (internal temperature 40° C.)
10. 10
    workup.ADDITIONFurther ethyl acetate (50 mL) was added
11. 11
    Temperaturinternal temperature was increased to 50° C.
12. 12
    workup.ADDITIONheptane (800 mL) was added slowly
13. 13
    SonstigeCrystallization
14. 14
    workup.ADDITIONafter addition of ca. 300 mL heptane
15. 15
    workup.STIRRINGThe suspension was stirred for 12 h at room temperature
16. 16
    Filtrationfiltered
17. 17
    WaschenThe crystals were washed with cold heptane (400 mL)
18. 18
    Sonstigedried in vacuo at 40° C.

Vorschrift

Methyl-cyclopropanecarboxylic acid (56.4 g, 552 mmol) was dissolved in dichloromethane (365 mL) and dimethylformamide (405 μl, 5.2 mmol) was added. The mixture was cooled to 2° C. and oxalyl chloride (70.8 g, 547 mmol) was added dropwise. It was allowed to warm and stirred for 90 min at room temperature. After that, it was added to a suspension of (1S,4S)-3-oxo-2-oxa-5-azonia-bicyclo[2.2.1]heptane methanesulfonate (110 g, 526 mmol) in dichloromethane (400 mL). The resulting suspension was cooled to 2° C. and triethylamine (256 mL, 1.84 mol) was added slowly (exothermic). After stirring for 70 min at room temperature, a solution of citric acid (81.0 g, 421 mmol) in water (550 mL) was added at 2° C. After separation of the phases, the aqueous phase was extracted with dichloromethane (300 mL). The combined organic extracts were washed with water (400 mL) and concentrated in vacuo to a volume of ca. 500 mL. Ethyl acetate (330 mL) was added and the residual dichloromethane was distilled off in vacuo (internal temperature 40° C.). Further ethyl acetate (50 mL) was added, internal temperature was increased to 50° C. and heptane (800 mL) was added slowly. Crystallization started after addition of ca. 300 mL heptane. The suspension was stirred for 12 h at room temperature and filtered. The crystals were washed with cold heptane (400 mL) and dried in vacuo at 40° C. to afford the title compound as colorless crystals (88.45 g, 86%). mp. 101-102° C. MS (ESI & APCI): m/z=196.1 [M+H]+. 1H NMR (CDCl3, 600 MHz); δ 0.60-0.67 (m, 2H), 0.87-0.91 (m, 1H), 1.13-1.17 (m, 1H), 1.39 (s, 3H), 2.04 (dd, J=1.2 Hz, 10.9 Hz, 1H), 2.32 (d, J=10.8 Hz, 1H), 3.59 and 3.69 (AB, JAB=11.5 Hz, each 1H), 4.97 (s, 1H), 5.18 (s, 1H).

Quelle