Diisopropylamine → 5-Bromo-2-fluoro-3-pyridinecarboxaldehyde

Temperature

-65 °C

To a solution of diisopropylamine (17 mL, 0.17 mol) in dry THF (200 mL) was added 2.5 M n-BuLi in hexane (68 mL, 0.17 mol) dropwise at 0° C. under N2 atmosphere. After the addition, the resulting mixture was cooled to −65° C. A solution of 5-bromo-2-fluoropyridine (25 g, 0.14 mol) in dry THF (100 mL) was then added dropwise. The resulting mixture was stirred at −65° C. for 90 minutes. Then ethyl formate (15.6 g, 0.21 mol) was added dropwise to the mixture. After stirred for 10 minutes, the reaction mixture was quenched with a solution of 10% citric acid in THF (100 mL) at −65° C. The resulting mixture was warmed up to room temperature, poured into water (100 mL) and extracted with EtOAc (200 mL). The organic layer was separated and washed with saturated aqueous NaCl (100 mL×2), dried over Na2SO4 and concentrated in vacuo to yield compound D-1-2 (25 g, 85%) as a yellow solid.

1. additionAfter the addition
2. stirringAfter stirred for 10 minutes
3. customthe reaction mixture was quenched with a solution of 10% citric acid in THF (100 mL) at −65° C
4. temperatureThe resulting mixture was warmed up to room temperature
5. additionpoured into water (100 mL)
6. extractionextracted with EtOAc (200 mL)
7. customThe organic layer was separated
8. washwashed with saturated aqueous NaCl (100 mL×2)
9. dry with materialdried over Na2SO4
10. concentrationconcentrated in vacuo
11. customto yield compound D-1-2 (25 g, 85%) as a yellow solid

ORD record

ord-1cb49a2a79a543eda1b605e2dcb7e374

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07772246B2