Methyl iodide → Methyl 2-(2-bromo-5-chlorophenyl)propanoate

Temperature

0 °C

A solution of n-butyllithium (1.67 mL of a 2.5 M solution in hexanes, 4.17 mmol) was added dropwise via syringe to a stirred solution of diisopropylamine (0.61 mL, 4.36 mmol) in tetrahydrofuran (10 mL) at −78° C. After approximately 10 min, the reaction mixture was warmed to 0° C. and aged for another 10 min. After re-cooling to −78° C., a solution of methyl (2-bromo-5-chlorophenyl)acetate (1-2) (1.00 g, 3.79 mmol) in tetrahydrofuran (10 mL) was added dropwise via syringe and the resulting yellow mixture was stirred at −78° C. for approximately 30 min. Iodomethane (0.35 mL, 5.69 mmol) was added and after 1 h, the reaction mixture was warmed to ambient temperature and quenched with saturated aqueous ammonium chloride. The resulting mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0-20% ethyl acetate/hexanes as eluent) furnished 2-1 as a colorless oil (1.00 g).

1. waitaged for another 10 min
2. temperatureAfter re-cooling to −78° C.
3. temperaturethe reaction mixture was warmed to ambient temperature
4. customquenched with saturated aqueous ammonium chloride
5. additionThe resulting mixture was poured into water
6. extractionextracted three times with ethyl acetate
7. washThe combined organic extracts were washed with brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 0-20% ethyl acetate/hexanes as eluent)

ORD record

ord-c5ae05a933ba4ff58fe8e06ebfc5fc6f

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06818658B2