反应 #48300

反应方程式

1-Iodo-4-(trifluoromethyl)benzene

dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl

Iodine

(R)-methyl 2-(tert-butoxycarbonyl)-3-iodopropanoate

→

(S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate

溶剂

DMF

反应条件

后处理

1. 1
   温度the solid mixture was heated under vacuum for 10 minutes
2. 2
   其他The flask was flushed with nitrogen three times
3. 3
   温度to cool
4. 4
   workup.ADDITIONDMF (0.5 mL, degassed with nitrogen) was added
5. 5
   workup.ADDITIONwas added dropwise
6. 6
   workup.WAITto come to RT for 30 minutes
7. 7
   其他The flask was purged with nitrogen
8. 8
   温度heated at 40° C
9. 9
   workup.WAITAfter 3 hours the reaction was allowed
10. 10
    温度to cool
11. 11
    其他partitioned between EtOAc
12. 12
    萃取The aqueous layer was extracted with EtOAc
13. 13
    洗涤the combined organic layers were washed with water, brine
14. 14
    干燥dried over sodium sulfate
15. 15
    浓缩Concentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc)

实验过程

Iodine (0.0140 g, 0.0553 mmol) was added to zinc (0.542 g, 8.29 mmol) and the solid mixture was heated under vacuum for 10 minutes. The flask was flushed with nitrogen three times and allowed to cool. DMF (0.5 mL, degassed with nitrogen) was added and the suspension was cooled to 0° C. and stirred while (R)-methyl 2-(tert-butoxycarbonyl)-3-iodopropanoate (1.82 g, 5.53 mmol) in DMF (2.8 mL) was added dropwise. The mixture was stirred for 30 minutes at 0° C. and then allowed to come to RT for 30 minutes. 1-Iodo-4-(trifluoromethyl)benzene (1.50 g, 5.53 mmol), tris(dibenzylideneacetone)dipalladium (0.101 g, 0.111 mmol), and dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-Phos) (0.182 g, 0.442 mmol) were added. The flask was purged with nitrogen and heated at 40° C. After 3 hours the reaction was allowed to cool and partitioned between EtOAc and an aqueous solution of ˜9:1 saturated ammonium chloride/ammonium hydroxide. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, brine, and dried over sodium sulfate. Concentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc) afforded (S)-methyl 2-(tert-butoxycarbonyl)-3-(4-(trifluoromethyl)phenyl)propanoate.

来源