반응 #1126843

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

5-bromo-2,2-difluorobenzo[d][1,3]dioxole

→

(S)-methyl 2-(tert-butoxycarbonyl)-3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propanoate

수율 52.3%

용매

DMF

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후처리

1. 1
   온도The mixture was heated with a heat gun for 5 minutes
2. 2
   기타the resulting mixture was then flushed with nitrogen 3 times
3. 3
   온도before being warmed to rt
4. 4
   workup.STIRRINGAfter stirring at rt for 30 minutes
5. 5
   온도the reaction mixture was heated to 40° C. for 2 hours
6. 6
   온도The resulting mixture was cooled to rt
7. 7
   기타partitioned between ethyl acetate (50 mL)
8. 8
   추출The aqueous layer was extracted with ethyl acetate (3×100 mL)
9. 9
   세척the combined organic layers were washed with water, brine
10. 10
    건조dried over sodium sulfate
11. 11
    기타Concentration of the filtered solvents and purification
12. 12
    기타of resulting crude material by silica gel chromatography

실험 절차

To a 25 mL RBF was added zinc powder (1.03 g, 15.8 mmol) and iodine (0.0161 g, 0.0633 mmol). The mixture was heated with a heat gun for 5 minutes and the resulting mixture was then flushed with nitrogen 3 times and allowed to cool to rt. A solution of (R)-methyl 2-(tert-butoxycarbonyl)-3-iodopropanoate (3.47 g, 10.5 mmol) in 5 mL of DMF was added dropwise to the mixture over 3 minutes and the resulting grey slurry was stirred at 0° C. for 20 minutes before being warmed to rt. After stirring at rt for 30 minutes, 5-bromo-2,2-difluorobenzo[d][1,3]dioxole (2.50 g, 10.5 mmol), Pd2(dba)3 (0.193 g, 0.211 mmol) and S(Phos) (0.346 g, 0.844 mmol) were added and the reaction mixture was heated to 40° C. for 2 hours. The resulting mixture was cooled to rt and partitioned between ethyl acetate (50 mL) and a solution of ˜9:1 saturated ammonium chloride/ammonium hydroxide pH=9 (250 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL) and the combined organic layers were washed with water, brine, and dried over sodium sulfate. Concentration of the filtered solvents and purification of resulting crude material by silica gel chromatography provided (S)-methyl 2-(tert-butoxycarbonyl)-3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)propanoate (1.89 g, 49.9% yield) as a slightly brown oil.

출처