تفاعل #48300

معادلة التفاعل

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

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe solid mixture was heated under vacuum for 10 minutes
2. 2
   أخرىThe flask was flushed with nitrogen three times
3. 3
   درجة الحرارةto 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
   أخرىThe flask was purged with nitrogen
8. 8
   درجة الحرارةheated at 40° C
9. 9
   workup.WAITAfter 3 hours the reaction was allowed
10. 10
    درجة الحرارةto cool
11. 11
    أخرىpartitioned between EtOAc
12. 12
    استخلاصThe aqueous layer was extracted with EtOAc
13. 13
    غسيلthe combined organic layers were washed with water, brine
14. 14
    تجفيفdried over sodium sulfate
15. 15
    تركيزConcentration and purification by silica gel chromatography (6:1 Hexanes/EtOAc)

الإجراء التجريبي

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.

المصدر