تفاعل #492219

معادلة التفاعل

(S)-5-cyclopropyl-4,4-difluoro-1-methoxy-1-oxopentan-2-amine hydrochloride

trifluoroacetophenone

potassium carbonate

methanol

→

(S)-5-cyclopropyl-4,4-difluoro-2-((S)-2,2,2-trifluoro-1-phenylethylamino)pentanoic acid

المردود 71.3%

المذيبات

acetonitrile

isopropanol

ظروف التفاعل

المعالجة

1. 1
   ترشيحwas filtered under hot and the solids
2. 2
   غسيلwere washed with isopropanol (20 mL)
3. 3
   تركيزconcentrated under reduced pressure
4. 4
   درجة الحرارةabove was cooled to −45° C.
5. 5
   workup.ADDITIONwas added drop-wise
6. 6
   workup.STIRRINGthe reaction was stirred at same temperature for 1 h
7. 7
   أخرىOnce the staring material was consumed
8. 8
   أخرىwas quenched with 1N HCl solution (10 mL) at 0° C.
9. 9
   درجة الحرارةto warm to room temperature
10. 10
    استخلاصThe mixture was extracted with ethyl acetate (3×40 mL)
11. 11
    غسيلthe combined organic extracts washed with water (50 mL) and brine (50 mL)
12. 12
    أخرىThe organic extracts were evaporated under reduced pressure
13. 13
    workup.DISSOLUTIONthe residue re-dissolved in ethyl acetate (20 mL)
14. 14
    غسيلwashed with water (20 mL) and brine (50 mL)
15. 15
    تجفيفThe solution was dried (MgSO4)
16. 16
    أخرىthe solvent evaporated under reduced pressure

الإجراء التجريبي

(S)-5-cyclopropyl-4,4-difluoro-1-methoxy-1-oxopentan-2-amine hydrochloride (250 mg, 10 mmol), trifluoroacetophenone (179 mg, 10 mmol), potassium carbonate (426 mg, 30 mmol) was charged in isopropanol (10 mL) under nitrogen. The reaction mixture stirred for 20 h at 60° C. When TLC showed an absence of starting material, is the mixture was filtered under hot and the solids were washed with isopropanol (20 mL) and the filtrates were combined and concentrated under reduced pressure. The residue (400 mg, 10 mmol) was dissolved in acetonitrile (5 mL) and methanol (1 mL) and transferred to a dropping funnel under nitrogen. The zinc borohydride suspension prepared as described above was cooled to −45° C. and treated with the imine solution which was added drop-wise and the reaction was stirred at same temperature for 1 h. Once the staring material was consumed, is the reaction mixture was quenched with 1N HCl solution (10 mL) at 0° C. and then allowed to warm to room temperature. The mixture was extracted with ethyl acetate (3×40 mL) and the combined organic extracts washed with water (50 mL) and brine (50 mL). The organic extracts were evaporated under reduced pressure, and the residue re-dissolved in ethyl acetate (20 mL) and washed with water (20 mL) and brine (50 mL). The solution was dried (MgSO4) and the solvent evaporated under reduced pressure to give (S)-5-cyclopropyl-4,4-difluoro-2-((S)-2,2,2-trifluoro-1-phenylethylamino)pentanoic acid as a pale oil (265 mg, 71.3%).

المصدر