反应详情

温度

75 °C

To a suspension of 2-(5-iodo-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide (Example 6) (36.0 g, 0.1 mol) in DME (250 mL), at 20° C. boron trifluoride etherate (28.3 g, 0.2 mol) is added. Under cooling with an ice bath, borane dimethyl sulfide complex (12.0 g, 0.15 mol) is added during 10 minutes, and then the cooling bath is removed. The temperature rises slowly to 55° C., and a suspension forms at about 50° C. When the exothermic reaction has subsided, the mixture is stirred at 75° C. for another 30 minutes, and then quenched by adding 4 N NaOH (100 mL). The mixture is heated under reflux for another 30 minutes, and then filtered while still hot. Removal of the solvent on the rotavapor leads to crystallization of the product, which goes to completion on standing in the refrigerator for 12 hours. The product is filtered off, washed with cold acetone (50 mL, −20° C.) and pentane, and dried to give the title product (24.8 g, 75%) as crystals, mp.=195-200° C. 1H-NMR (DMSO-D6, 300 MHz) δ 2.80, 2.99 (2 s, 3H each, N(CH3)2); 3.69 (s, 2H, CH2); 7.19 (d, 1H, 3J=2.4 Hz, H-2); 7.21 (d, 1H, 3J=8.5 Hz, H-7); 7.32 (dd, 1H, 4J=1.7 Hz, H-6); 7.92 (d, 1H, H-4); 11.04 (br s, 1H, NH). 13C-NMR (DMSO-D6, 75 MHz) δ 31.11 (CH2); 35.70, 37.91 (N(CH3)3); 82.82 (C-5); 108.54 (C-3); 114.51 (C-7); 125.46 (C-2); 128.16 (C-4); 129.54 (C-6); 130.85 (C-9); 135.91 (C-8).

1. temperatureUnder cooling with an ice bath
2. additionborane dimethyl sulfide complex (12.0 g, 0.15 mol) is added during 10 minutes
3. customthe cooling bath is removed
4. customrises slowly to 55° C.
5. customat about 50° C
6. customWhen the exothermic reaction
7. customquenched
8. additionby adding 4 N NaOH (100 mL)
9. temperatureThe mixture is heated
10. temperatureunder reflux for another 30 minutes
11. filtrationfiltered while still hot
12. customRemoval of the solvent on the rotavapor
13. customleads to crystallization of the product, which
14. waiton standing in the refrigerator for 12 hours
15. filtrationThe product is filtered off
16. washwashed with cold acetone (50 mL, −20° C.) and pentane
17. customdried