反应详情

To a solution of 2-fluoro-4-(morpholino)-benzonitrile (2.82 g, 13.7 mmol) in tetrahydrofuran (27 ml) under a nitrogen atmosphere was added dropwise a 1.5 M solution of DIBAL-H in toluene (18.3 ml, 27.3 mmol) during 13 minutes and the resulting mixture stirred for 23.5 hr at room temperature. The mixture was cooled to −50° C. and the excess DIBAL-H destroyed by careful addition of methanol (27 ml). The mixture was then stirred at room temperature for 10 mins, saturated ammonium chloride (27 ml) added and the resulting mixture stirred at room temperature for 40 mins., and then evaporated under reduced pressure to a yellow solid. This solid was partitioned between dichloromethane (120 ml) and water (120 ml) and solid potassium carbonate added until the aqueous phase was pH 10. The phases were separate via a hydrophobic frit and the organic phase evaporated and the residue purified by a Biotage™ column (40 g, silica) eluting with cyclohexane:ethyl acetate: (7:3) to give 2-fluoro-4-(morpholino)-benzaldehyde (1.96 g, 68%) as a white solid.

1. temperatureThe mixture was cooled to −50° C.
2. customthe excess DIBAL-H destroyed by careful addition of methanol (27 ml)
3. stirringThe mixture was then stirred at room temperature for 10 mins
4. additionsaturated ammonium chloride (27 ml) added
5. stirringthe resulting mixture stirred at room temperature for 40 mins
6. custom, and then evaporated under reduced pressure to a yellow solid
7. customThis solid was partitioned between dichloromethane (120 ml) and water (120 ml) and solid potassium carbonate
8. additionadded until the aqueous phase
9. customThe phases were separate via a hydrophobic frit
10. customthe organic phase evaporated
11. customthe residue purified by a Biotage™ column (40 g, silica)
12. washeluting with cyclohexane