Reaktion #631999

Reaktionsgleichung

sodium phosphate

NaOH

NaOH

NaOH

(1S,2R)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester

→

(1R,2S)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester

Lösungsmittel

water

water

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added 511 grams of Alcalase 2.4 L (about 425 mL) (Novozymes North America Inc.)
2. 2
   Sonstigereached 39° C.
3. 3
   TemperaturThe reaction temperature was maintained at 40° C. for 24.5 hours during which time the pH of the mixture
4. 4
   Sonstigewas adjusted to 8.0 at the 1.5 hour and 19.5 hour time points
5. 5
   Temperaturthe reaction was cooled to room temperature (26° C.)
6. 6
   Extraktionthe resulting mixture was extracted with MTBE (2×2 L)
7. 7
   ExtraktionThe combined MTBE extract
8. 8
   Waschenwas washed with 5% NaHCO3 (3×100 mL), water (3×100 mL)
9. 9
   Einengenconcentrated in vacuo

Vorschrift

To an aqueous solution of sodium phosphate buffer (0.1M, 4.25 L, pH 8) housed in a 12 Liter jacked reactor, maintained at 39° C., and stirred at 300 rpm, was added 511 grams of Alcalase 2.4 L (about 425 mL) (Novozymes North America Inc.). When the temperature of the mixture reached 39° C., the pH was adjusted to 8.0 by the addition of 50% NaOH in water. A solution of (1R,2S)/(1S,2R)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester (85 g) in 850 mL of DMSO was then added over a period of 40 minutes. The reaction temperature was maintained at 40° C. for 24.5 hours during which time the pH of the mixture was adjusted to 8.0 at the 1.5 hour and 19.5 hour time points using 50% NaOH in water. After 24.5 hours, the enantio-excess of the ester was determined to be 97.2%, and the reaction was cooled to room temperature (26° C.) and stirred overnight (16 hours) at which time the enantio-excess of the ester was determined to be 100%. The pH of the reaction mixture was then adjusted to 8.5 with 50% NaOH and the resulting mixture was extracted with MTBE (2×2 L). The combined MTBE extract was washed with 5% NaHCO3 (3×100 mL), water (3×100 mL), and then concentrated in vacuo to give the enantiomerically pure (1R,2S)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester as light yellow solid (42.55 g; purity: 97% (210 nm, containing no acid; 100% enantiomeric excess (“ee”).

Quelle