P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].[OH-].[Na+].[CH2:11]([O:13][C:14]([C@:16]1([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C@@H:17]1[CH:19]=[CH2:20])=[O:15])[CH3:12]>O.CS(C)=O>[CH2:11]([O:13][C:14]([C@@:16]1([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:18][C@H:17]1[CH:19]=[CH2:20])=[O:15])[CH3:12]
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”).
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