反应 #632000

反应方程式

DI water

NaOH

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

NaOH

NaOH

sodium borate

NaOH

→

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

溶剂

DMSO

反应条件

后处理

1. 1
   其他at 45° C.
2. 2
   其他When the temperature of the mixture closed to 45° C.
3. 3
   其他was then adjusted to 48° C
4. 4
   workup.WAITAt 18 hours
5. 5
   workup.WAITAt 24 hours the temperature was lowered to 35° C
6. 6
   温度Heating
7. 7
   workup.WAITwas stopped at 48 hours
8. 8
   温度the reaction was slowly cooled down to room temperature (about 25° C.)
9. 9
   workup.STIRRINGstirred overnight
10. 10
    workup.WAITAt 66 hours
11. 11
    萃取The mixture was extracted with MTBE (2×4 L)
12. 12
    洗涤The combined MTBE extracts were washed with 5% NaHCO3 (6×300 mL) and water (3×300 mL)
13. 13
    浓缩concentrated

实验过程

A solution of 5 L of 0.2M sodium borate buffer (pH 9) at 45° C. in a 20 L jacked reactor stirred at 400 rpm was treated with 3 L of DI water and 4 L of Savinase 16 L, type EX (Novozymes North America Inc.). When the temperature of the mixture closed to 45° C., the pH was adjusted to 8.5 with 10N NaOH. A solution of (1R,2S)/(1S,2R)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester (200 grams) in 2 L DMSO was added to the reactor over a period of 40 minutes via addition funnel. The reaction temperature was then adjusted to 48° C. After 2 hours, the pH was adjusted to pH 9.0 with 10N NaOH. At 18 hours, enantio-excess of the ester reached 72% and the pH was adjusted to 9.0 with 10N NaOH. At 24 hours the temperature was lowered to 35° C. At 42 hours the temperature was raised to 48° C. and the pH was adjusted to 9.0 with 10N NaOH. Heating was stopped at 48 hours and the reaction was slowly cooled down to room temperature (about 25° C.) and stirred overnight. At 66 hours, the pH of the reaction mixture was 8.6. The mixture was extracted with MTBE (2×4 L). The combined MTBE extracts were washed with 5% NaHCO3 (6×300 mL) and water (3×300 mL) and concentrated to give enantiomerically pure (1R,2S)N-Boc-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester as light yellow crystals (101A g; purity: 95.9% (210 nm, containing no acid; 98.6% ee).

来源