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

반응식

HRID 1176334 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3f95a6e8a441496295f034ff84a9e058
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842688B2

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