反应详情

温度

-50 °C

A solution of 3-fluoro-5-bromopyridine carboxylic acid methoxymethylamide (630 mg, 2.4 mmol) in dry THF (12 mL) was cooled to −50° C. and DIBAL (1M in THF; 2.8 mL, 2.8 mmol) was added over 15 min maintaining the temperature below −50° C. The reaction was stirred at −50° C. for 2 h. An additional portion of and DIBAL (1M in THF; 0.25 mL, 0.25 mmol) was added and the reaction mixture was allowed to warm slowly to −10° C. over 2 h. The reaction was quenched by the dropwise addition of water (5 mL) and the THF was removed in vacuo and a dilute solution of Rochelle's salt was added. The aqueous was extracted with EtOAc (×3) and the combined organics dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (gradient: 10%-90% EtOAc in petroleum ether 40-60c) yielded 3-fluoro-5-bromopyridine-2-carbaldehyde as a yellow solid.

1. temperaturemaintaining the temperature below −50° C
2. temperatureto warm slowly to −10° C. over 2 h
3. customThe reaction was quenched by the dropwise addition of water (5 mL)
4. customthe THF was removed in vacuo
5. additiona dilute solution of Rochelle's salt was added
6. extractionThe aqueous was extracted with EtOAc (×3)
7. dry with materialthe combined organics dried (MgSO4)
8. concentrationconcentrated in vacuo
9. customPurification by column chromatography (gradient: 10%-90% EtOAc in petroleum ether 40-60c)