Reaktion #2490075

Reaktionsgleichung

hydrochloric acid

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

1-amino-cyclopropanecarbonitrile hydrochloride

sodium 2-ethylhexanoate

sodium chloride

→

title compound

Ausbeute 91.1%

(2S,4S)-4-hydroxy-1-(1-methyl-cyclopropanecarbonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide

Ausbeute 91.1%

Lösungsmittel

dichloromethane

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   workup.STIRRINGThe mixture was stirred for 1 h
3. 3
   Sonstigephases were separated
4. 4
   Extraktionthe aqueous layer was extracted with dichloromethane (3×330 mL)
5. 5
   Einengenthe combined organic extracts were concentrated in vacuo to a volume of ca. 1.1 L
6. 6
   workup.ADDITIONEthyl acetate (1.1 L) was added
7. 7
   Einengenthe mixture was concentrated in vacuo to a volume of ca. 1 L and heptane (1 L)
8. 8
   workup.ADDITIONwas added within 30 min
9. 9
   workup.STIRRINGThe resulting suspension was stirred for 2 h at 2° C.
10. 10
    Filtrationfiltered
11. 11
    Waschenthe precipitate was washed with cold ethyl acetate/heptane 1:1 (v/v, 340 mL) and heptane (340 mL)
12. 12
    Sonstigedried in vacuo

Vorschrift

(1S,4S)-5-(1-Methyl-cyclopropanecarbonyl)-2-oxa-5-aza-bicyclo[2.2.1]heptan-3-one (100 g, 512 mmol), 1-amino-cyclopropanecarbonitrile hydrochloride (62.0 g, 523 mmol), and sodium 2-ethylhexanoate (97%, 96.5 g, 563 mmol) were dissolved in water (500 mL). The mixture was stirred for 16 h at 50° C. After cooling to room temperature, dichloromethane (500 mL) was added, the mixture was acidified by addition of hydrochloric acid (25% m/m, 13.8 mL, 106 mmol), and sodium chloride (120 g) was added. The mixture was stirred for 1 h, phases were separated, the aqueous layer was extracted with dichloromethane (3×330 mL) and the combined organic extracts were concentrated in vacuo to a volume of ca. 1.1 L. Ethyl acetate (1.1 L) was added, the mixture was concentrated in vacuo to a volume of ca. 1 L and heptane (1 L) was added within 30 min. The resulting suspension was stirred for 2 h at 2° C., filtered, the precipitate was washed with cold ethyl acetate/heptane 1:1 (v/v, 340 mL) and heptane (340 mL) and dried in vacuo to afford the title compound as light yellow crystals (129.4 g, 90%). MS (ESI & APCI): m/z=278.1 [M+H]+. 1H NMR (CDCl3, 600 MHz): δ 0.60-0.65 (m, 2H), 0.89-0.92 (m, 1H), 0.95-0.98 (m, 1H), 1.20-1.26 (m, 2H), 1.33 (s, 3H), 1.50-1.57 (m, 2H), 2.13 (ddd, J=5.0 Hz, 9.0 Hz, 14.1 Hz, 1H), 2.39 (br d, J=14.3 Hz, 1H), 3.76 (dd, J=4.3 Hz, 11.6 Hz, 1H), 3.85 (d, J=11.6 Hz, 1H), 4.48-4.53 (m, 1H), 4.57 (d, J=9.0 Hz, 1H), 4.70 (br s, 1H), 7.92 (br s, 1H).

Quelle