反应详情

A solution of sodium nitrite (2.07 g, 30.0 mmol) in water (6.0 mL) was added dropwise to an ice cold slurry of 3-amino-4-chlorophenol (4.30 g, 30.0 mmol) and hydrochloric acid (37% aqueous, 9.0 mL) and the mixture stirred for 45 min. Tin (II) chloride (15.4 g, 81.0 mmol) in water (18.0 mL) and hydrochloric acid (37% aqueous, 18.0 mL) was added dropwise and the reaction stirred overnight. The mixture was cooled in an ice/water bath, diluted with water and neutralised by addition of NaOH (1M aq). The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was passed through an acidic ion-exchange cartridge (SCX-2), washing with methanol and eluting with 2M ammonia in methanol. The basic fraction was evaporated in vacuo then purified by FCC, using 3-10% [2M NH3 in MeOH] in DCM, to give the title compound (1.30 g, 27%). 1H NMR (300 MHz, d6-DMSO): 4.12 (2H, br s), 6.03 (1H, dd, J=8.5, 2.9 Hz), 6.26 (1H, s), 6.63 (1H, d, J=2.7 Hz), 6.93 (1H, d, J=8.5 Hz), 9.22 (1H, s).

1. stirringthe reaction stirred overnight
2. temperatureThe mixture was cooled in an ice/water bath
3. extractionThe aqueous layer was then extracted with EtOAc (3×)
4. washThe combined organic layers were washed with brine
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. washwashing with methanol
9. washeluting with 2M ammonia in methanol
10. customThe basic fraction was evaporated in vacuo
11. customthen purified by FCC