Diisopropylamine → methyl 2-(5-bromopyridin-2-yl)-2-methylpropanoate

Temperature

-10 °C

Diisopropylamine (0.45 ml, 3.17 mmol) was dissolved in THF (10 ml) under a nitrogen atmosphere and cooled to −10° C. n-BuLi (2.64 ml, 3.17 mmol, 1.2M solution in THF) was added dropwise over 5 minutes. The reaction mixture was stirred at −10° C. for 30 minutes, after which time the reaction mixture was cooled to −78° C. Methyl isobutyrate (0.36 ml, 3.17 mmol) was added dropwise over 5 minutes. Stirring was continued at −78° C. for 45 minutes. 2,5-Dibromopyridine (0.5 g, 2.11 mmol) in THF (10 ml) was added and the mixture allowed to warm to room temperature and stirred for 2 hours. The reaction was quenched by addition of saturated aqueous ammonium chloride solution, extracted into DCM (3×20 ml), the combined organics dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by FCC on silica gel [19:1 heptane/EtOAc as eluent] to provide the title compound as colourless oil (195 mg, 36%).

1. additionwas added dropwise over 5 minutes
2. temperatureafter which time the reaction mixture was cooled to −78° C
3. stirringStirring
4. waitwas continued at −78° C. for 45 minutes
5. temperatureto warm to room temperature
6. stirringstirred for 2 hours
7. customThe reaction was quenched by addition of saturated aqueous ammonium chloride solution
8. extractionextracted into DCM (3×20 ml)
9. dry with materialthe combined organics dried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by FCC on silica gel [19:1 heptane/EtOAc as eluent]

ORD record

ord-a821b3db1c0a453f8c9407117eddb387

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691804B2