Sodium hydride → Methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

HRID 513194ノート

反応式

HRID 513194 の反応式
[Cl:1][C:2]1[C:7]2[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[H-].[Na+].Br[CH2:18][CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=1>CN(C=O)C.O>[Cl:1][C:2]1[C:7]2[CH:8]=[C:9]([C:11]([O:13][CH3:14])=[O:12])[N:10]([CH2:18][CH2:19][O:20][C:21]3[CH:22]=[CH:23][C:24]([O:27][C:28]([F:29])([F:30])[F:31])=[CH:25][CH:26]=3)[C:6]=2[CH:5]=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 136722741-(2-Bromoethoxy)-4-(trifluoromethoxy)benzeneHCID 26599236methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

生成物 1

HCID 86720572Methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate収率 71.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
60 °C

実験手順

To a solution of Methyl 4-chloro-1H-pyrrolo[3,2-c]pyridine-2-carboxylate (350 mg, 1.662 mmole) in DMF (6 mL) was added NaH (60% dispersion in mineral oil, 86 mg, 2.160 mmole) portionwise at RT. After gas evolution had ceased a solution of 1-(2-bromoethoxy)-4-(trifluoromethoxy)benzene (616 mg, 2.160 mmole) in DMF (1 mL) was added. After the addition was complete the mixture was heated to 60° C. After 4 hr the mixture was cooled to RT. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic layers were washed with H2O and brine, dried (MgSO4), filtered, and concentrated. Flash column (Biotage-SNAP-25 g SiO2, 30% EtOAc/hexanes) gave the title compound (492 mg, 71%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.21 (d, J=6.0 Hz, 1 H); 7.45 (s, 1 H); 7.42 (d, J=6.0 Hz, 1 H); 7.07 (d, J=8.6 Hz, 2 H); 6.76-6.70 (m, 2 H); 4.93 (t, J=5.13 Hz, 2 H); 4.34 (t, J=5.0 Hz, 3 H); 3.95 (s, 3 H).

後処理

  1. additionwas added
  2. additionAfter the addition
  3. temperatureAfter 4 hr the mixture was cooled to RT
  4. extractionextracted with EtOAc (3×)
  5. washThe combined organic layers were washed with H2O and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-f78606f5918345cb88f4b3f44254f4c6
出典データセット
uspto-grants-2015_08
特許番号
US09102673B2

反応ノート

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