Chloroacetonitrile → benzyl 3-(7-bromo-1-cyanomethyl-3-methyl-1H-indol-6-ylmethoxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

HRID 1176334

反応式

HRID 1176334 の反応式
[Br:1][C:2]1[C:3]([CH2:12][O:13][CH:14]2[CH:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[O:38][CH3:39])=[CH:22][CH:21]=3)[CH2:18][CH2:17][N:16]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[CH2:15]2)=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH3:11].[H-].[Na+].Cl[CH2:53][C:54]#[N:55].[Cl-].[NH4+]>CN1C(=O)N(C)CCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:1][C:2]1[C:3]([CH2:12][O:13][CH:14]2[CH:19]([C:20]3[CH:21]=[CH:22][C:23]([O:26][CH2:27][CH2:28][CH2:29][O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[O:38][CH3:39])=[CH:24][CH:25]=3)[CH2:18][CH2:17][N:16]([C:40]([O:42][CH2:43][C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)=[O:41])[CH2:15]2)=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:53][C:54]#[N:55])[CH:8]=[C:7]2[CH3:11]

参加物

7

反応物 4

HCID 7856ChloroacetonitrileHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 68499829benzyl 3-(7-bromo-3-methyl-1H-indol-6-ylmethoxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

生成物 1

HCID 68501271benzyl 3-(7-bromo-1-cyanomethyl-3-methyl-1H-indol-6-ylmethoxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-溶媒

反応条件

温度
0 °C

実験手順

The solution of 3.38 g of benzyl 3-(7-bromo-3-methyl-1H-indol-6-ylmethoxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate (Example 21b) in 46 ml of DMPU is admixed with stirring at 0° C. with 0.367 g of sodium hydride dispersion (60%). The mixture is stirred at 0° C. over 30 minutes and then admixed with 0.323 ml of chloroacetonitrile and 0.172 g of tetrabutylammonium iodide. The reaction mixture is stirred at room temperature over 16 hours, poured onto 1M ammonium chloride solution and extracted with tert-butyl methyl ether (2×300 ml). The organic phases are washed successively with water (300 ml) and brine (300 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a white foam from the residue by means of flash chromatography (SiO2 60F). Rf=0.33 (1:1 EtOAc-heptane); Rt=6.10.

後処理

  1. stirringThe reaction mixture is stirred at room temperature over 16 hours
  2. extractionextracted with tert-butyl methyl ether (2×300 ml)
  3. washThe organic phases are washed successively with water (300 ml) and brine (300 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation

出典と根拠

ORDレコード
ord-3f95a6e8a441496295f034ff84a9e058
出典データセット
uspto-grants-2010_11
特許番号
US07842688B2

関連ノート

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