Boron trifluoride etherate → 2-(5-iodo-1H-indol-3-yl)-N,N-dimethyl-acetamide

HRID 2370422ノート

反応式

HRID 2370422 の反応式
O[C:2]1([CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([I:11])[CH:9]=2)[NH:4][C:3]1=O.B(F)(F)F.CCOCC>COCCOC>[I:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[NH:4][CH:3]=[C:2]2[CH2:13][C:14]([N:16]([CH3:17])[CH3:18])=[O:15]

参加物

4

反応物 2

HCID 8000Boron trifluoride etherateHCID 591297532-(3-Hydroxy-5-iodo-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

生成物 1

HCID 102459112-(5-iodo-1H-indol-3-yl)-N,N-dimethyl-acetamide収率 75.6%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
75 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-695fda3193e748008383941bc23f2ca9
出典データセット
uspto-grants-2014_04
特許番号
US08710093B2

反応ノート

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