反応 #88820

反応方程式

toluene

carbonate

di-isopropyl ethyl amine

L-tert-leucine

hydrochloric acid

→

VII

(S)-2-((((1R,2R)-2-allylcyclopropoxy)carbonyl)amino)-3,3-dimethylbutanoic acid (S)-1-Phenylethan-1-amine Salt

反応条件

後処理

1. 1
   その他in the reaction
2. 2
   その他reaction volume up to 60 mL
3. 3
   温度The reaction was then cooled to room temperature
4. 4
   workup.STIRRINGThe biphasic mixture was agitated for about 30 min at room temperature
5. 5
   その他the phases were split
6. 6
   濃縮The organic rich stream was then concentrated to approximately 20 mL by rotary evaporation
7. 7
   workup.ADDITION80 mL of acetonitrile was added
8. 8
   濃縮Concentration down to 20 mL
9. 9
   温度heated to about 50° C
10. 10
    温度The mixture is then heated to about 50° C.
11. 11
    workup.ADDITION(S)-phenethylamine (6.0 g, 49.7 mmol as a solution in 30 mL of acetonitrile at 50° C.) was charged
12. 12
    workup.WAITthe thin slurry was aged for 1 h at 50° C
13. 13
    温度The mixture was then cooled down to room temperature over about 3 h
14. 14
    その他was aged for at least about 12 h
15. 15
    ろ過The solids were collected by filtration
16. 16
    洗浄the cake was washed with about 20 mL of acetonitrile
17. 17
    その他The final wet cake was dried in the oven at about 40° C. under vacuum

実験手順

To a reaction vessel was charged a toluene solution of carbonate O (the amount of solution charged was determined by obtaining a wt % by 1H NMR of the carbonate in solution and then charging the amount necessary to have 9.9 g, 41.4 mmol of carbonate O in the reaction.). Additional toluene was charged to the reaction to bring the final reaction volume up to 60 mL. To this solution was charged di-isopropyl ethyl amine (10.7 g, 82.8 mmol) and L-tert-leucine (6.0 g, 45.52 mmol). The reaction mixture was heated to about 45° C. and agitated at this temperature for about 6 h. The reaction was then cooled to room temperature and hydrochloric acid (60 mL of a 3N aqueous solution) was charged. The biphasic mixture was agitated for about 30 min at room temperature and then the phases were split. The organic rich stream was then concentrated to approximately 20 mL by rotary evaporation and then 80 mL of acetonitrile was added. Concentration down to 20 mL and then recharging of acetonitrile was continued until the amount of toluene is about <5% v/v. The final stream is adjusted to a volume of 80 mL using acetonitrile and heated to about 50° C. The mixture is then heated to about 50° C. and (S)-phenethylamine (6.0 g, 49.7 mmol as a solution in 30 mL of acetonitrile at 50° C.) was charged. The reaction mixture was seeded with 0.5 wt % seeds of VII (0.05 g) and the thin slurry was aged for 1 h at 50° C. The mixture was then cooled down to room temperature over about 3 h and the resulting slurry was aged for at least about 12 h. The solids were collected by filtration and the cake was washed with about 20 mL of acetonitrile. The final wet cake was dried in the oven at about 40° C. under vacuum to afford VII.

出典