反应详情

To a suspension of methyl 4-amino-2-fluorobenzoate hydrochloride (Preparation 12, 33.2 g, 0.154 mmol, 1 eq) in a 1:1 mixture of concentrated HCl and water (70 ml:70 ml) cooling in an ice bath was added a solution of sodium nitrite (11.71 g, 0.169 mol, 1.1 eq) in warm water (20 ml) dropwise maintaining the temperature below 50° C. The reaction mixture was allowed to stir for 10 minutes then filtered through a pad of Celite and the solid washed with water. The filtrate was added portionwise to a solution of sulphur dioxide (49.4 g, 0.771 mol, 5 eq) and copper (1) chloride (100 mg) in AcOH (120 ml) at 0° C. and the reaction mixture stirred for 30 minutes. The mixture was extracted with DCM (3×150 ml), washed with saturated sodium hydrogen carbonate, water and brine, dried over magnesium sulphate, filtered and evaporated in vacuo. The crude material was purified by column chromatography eluting with 10% ethyl acetate:hexane to yield the title compound as a red oil (19.68 g, 0.078 mol, 50%).

1. temperaturecooling in an ice bath
2. temperaturedropwise maintaining the temperature below 50° C
3. filtrationthen filtered through a pad of Celite
4. washthe solid washed with water
5. stirringthe reaction mixture stirred for 30 minutes
6. extractionThe mixture was extracted with DCM (3×150 ml)
7. washwashed with saturated sodium hydrogen carbonate, water and brine
8. dry with materialdried over magnesium sulphate
9. filtrationfiltered
10. customevaporated in vacuo
11. customThe crude material was purified by column chromatography
12. washeluting with 10% ethyl acetate