反应详情

Oxalyl chloride (571 mg, 4.5 mmol) was added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (available from AK Scientific Product Catalog; 800 mg, 3.90 mmol) in dichloromethane (15 ml) followed by DMF (catalytic amount). The reaction mixture was stirred for 45 minutes, further oxalyl chloride (0.1 ml) and DMF (1 drop) were added and stirring continued for 20 minutes. The solvent was evaporated, the residue was co-evaporated with toluene then dried under high vacuum for 30 minutes. The crude acid chloride was dissolved in acetonitrile (10 ml) and added to a suspension of 1,1-dimethylethyl 6-[(hydroxyamino)(imino)methyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 17; 916 mg, 3.00 mmol) and triethylamine (607 mg, 6.00 mmol) in acetonitrile (15 ml). The reaction mixture was stirred at room temperature for 40 minutes then heated under reflux for 24 hours. The reaction mixture was cooled and the solvent evaporated. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase was separated, washed with brine, dried (MgSO4) and evaporated to give the crude product (1.3 g). The residue was purified by chromatography, eluting with 8-38% ethyl acetate in cyclohexane, to give the title compound (486 mg).

1. stirringstirring
2. waitcontinued for 20 minutes
3. customThe solvent was evaporated
4. customthen dried under high vacuum for 30 minutes
5. dissolutionThe crude acid chloride was dissolved in acetonitrile (10 ml)
6. stirringThe reaction mixture was stirred at room temperature for 40 minutes
7. temperaturethen heated
8. temperatureunder reflux for 24 hours
9. temperatureThe reaction mixture was cooled
10. customthe solvent evaporated
11. customThe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
12. customThe organic phase was separated
13. washwashed with brine
14. dry with materialdried (MgSO4)
15. customevaporated
16. customto give the crude product (1.3 g)
17. customThe residue was purified by chromatography
18. washeluting with 8-38% ethyl acetate in cyclohexane