1,2-Dibromoethane → Methyl 4-bromomethyl-3-cyanobenzoate

온도

70 °C

A suspension of zinc dust (792 mg, 12.12 mmol) and 1,2-dibromoethane (44 μL, 0.51 mmol) in THF (3 mL) was stirred at 70° C. for 10 minutes. The mixture was cooled to room temperature and chlorotrimethylsilane (45 μL, 0.36 mmol) was added. The mixture was cooled to 0° C. and a solution of methyl-4(bromomethyl)benzoate (2.314 g, 10.10 mmol) in THF (11 mL) was added at 0° C. over 2 hours and then stirred for an additional 2 hours at 0° C. The reaction mixture was cooled to −78° C. and a solution of tosyl cyanide (1.556 g, 8.59 mmol) in THF (11 mL) was added and the resultant mixture stirred at room temperature for 16 hours. The mixture was concentrated under reduced pressure, diluted with CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (15 mL) and filtered. The phases were separated and the aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (Hexanes/EtOAc, 10:1) afforded the desired nitrile (973 mg) as a 16:1 mixture (desired product/side product).

1. temperatureThe mixture was cooled to room temperature
2. temperatureThe mixture was cooled to 0° C.
3. stirringstirred for an additional 2 hours at 0° C
4. temperatureThe reaction mixture was cooled to −78° C.
5. concentrationThe mixture was concentrated under reduced pressure
6. additiondiluted with CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (15 mL)
7. filtrationfiltered
8. customThe phases were separated
9. extractionthe aqueous layer was extracted with CH2Cl2 (3×50 mL)
10. dry with materialThe combined organic extracts were dried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customPurification by column chromatography on silica gel (Hexanes/EtOAc, 10:1)

ORD 기록

ord-f80a5334ac5b44c6a4a92482bc07ca01

출처 데이터셋

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06734191B2