Реакция #48300

Уравнение реакции

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

Растворители

DMF

Условия реакции

Обработка

1. 1
   Температураthe solid mixture was heated under vacuum for 10 minutes
2. 2
   ДругоеThe flask was flushed with nitrogen three times
3. 3
   Температураto 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
   ДругоеThe flask was purged with nitrogen
8. 8
   Температураheated at 40° C
9. 9
   workup.WAITAfter 3 hours the reaction was allowed
10. 10
    Температураto cool
11. 11
    Другоеpartitioned between EtOAc
12. 12
    ЭкстракцияThe aqueous layer was extracted with EtOAc
13. 13
    Промывкаthe combined organic layers were washed with water, brine
14. 14
    Сушкаdried over sodium sulfate
15. 15
    КонцентрированиеConcentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc)

Методика

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.

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