Ethyl chloroformate → Ethyl 4-bromo-2-chloronicotinate

Temperature

-78 °C

To a solution of 4-bromo-2-chloropyridine (21.2 mmol) in 60 mL THF was added dropwise 11.7 mL of a solution of LDA (2M in THF) at −78° C. After stirring at −78° C. for 35 min, a solution of ethyl chloroformate (20.7 mmol) in 5 mL THF was added and the mixture was stirred at −78° C. for 2 h. The reaction was quenched with sat. aq. NaHCO3 solution and extracted with EtOAc (3×). The combined organic layers were dried over MgSO4 and concentrated in vacuo. Purification by (KP-SIL™ from Biotage) using Hept to Hept/EtOAc (8/2) gives the desired product as brown oil;

1. stirringthe mixture was stirred at −78° C. for 2 h
2. customThe reaction was quenched with sat. aq. NaHCO3 solution
3. extractionextracted with EtOAc (3×)
4. dry with materialThe combined organic layers were dried over MgSO4
5. concentrationconcentrated in vacuo
6. customPurification by (KP-SIL™ from Biotage)

ORD record

ord-6e27d7ad34cb4800af60a544e2bbeb02

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221832B2