反应详情

A slurry of 8-nitro-3-phenylsulfonylquinoline (D4) (46.7 g, 172 mmol), in tetrahydrofuran (750 ml) was added to a stirred solution of 30% titanium (III) chloride in aqueous HCl (470 ml) [Supplied by BDH] cooled in an ice bath, at such a rate that the temperature was maintained below 35° C. Once the addition was completed, the solution was stirred for a further 10 minutes then water (1.5 L) was introduced and the mixture poured into a 5 L beaker. The rapidly stirred solution was treated by portionwise addition of solid potassium carbonate in order to attain pH ˜8.5. EDTA (250 g, 0.86 mol) was added and followed by further potassium carbonate to maintain pH ˜8.5. The mixture was extracted with dichloromethane (3×1 L) and the combined organic phase passed through a silica plug (500 g) eluting with further dichloromethane (1 L) and 10% ethyl acetate in dichloromethane (1 L). The combined organic phases were evaporated and the residue subjected to purification using Biotage Flash-75 chromatography apparatus (2 kg silica gel), eluting with dichloromethane and increasing proportions of ether to give the title compound (D5) (34.5 g, 72%) as a pale brown solid;

1. temperaturecooled in an ice bath
2. temperatureat such a rate that the temperature was maintained below 35° C
3. additionOnce the addition
4. additionthe mixture poured into a 5 L beaker
5. temperatureto maintain pH ˜8.5
6. extractionThe mixture was extracted with dichloromethane (3×1 L)
7. washeluting with further dichloromethane (1 L) and 10% ethyl acetate in dichloromethane (1 L)
8. customThe combined organic phases were evaporated
9. customthe residue subjected to purification
10. washchromatography apparatus (2 kg silica gel), eluting with dichloromethane
11. temperatureincreasing proportions of ether