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Potassium bis(trimethylsilyl)amide → 2,6-Dimethyl-4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid ethyl ester

HRID 1630787
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HRID 1630787 반응식
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[C:6]2[CH3:18].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:29]([O:31][C:32](=[O:43])[C:33]1[C:38]([CH3:39])=[CH:37][C:36]([CH2:40]Br)=[CH:35][C:34]=1[CH3:42])[CH3:30]>C1COCC1>[CH2:29]([O:31][C:32](=[O:43])[C:33]1[C:38]([CH3:39])=[CH:37][C:36]([CH2:40][N:8]2[C:9]3[C:5](=[CH:4][C:3]([Cl:2])=[CH:11][CH:10]=3)[C:6]([CH3:18])=[C:7]2[C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[CH:35][C:34]=1[CH3:42])[CH3:30]
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참가 물질

5

반응물 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539625-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochlorideHCID 582156744-Bromomethyl-2,6-dimethyl-benzoic acid ethyl ester

생성물 1

HCID 582156242,6-Dimethyl-4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid ethyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran
용매
2회

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온도
0 °C

실험 절차

5-Chloro-3-methyl-2-pyridin-3-yl-1H-indole (Example 2, 1.350 g, 4.659 mmol) is suspended in THF (40 mL) and cooled to 0° C. KHMDS (0.5M in toluene, 32.6 mL, 16.3 mmol) is added dropwise. After 1 h, 4-bromomethyl-2,6-dimethyl-benzoic acid ethyl ester (4.95 g, 18.2 mmol) in THF (10 mL) is added dropwise. The mixture is allowed to warm to room temperature overnight. The mixture is then quenched with saturated aqueous ammonium chloride and diluted with dichloromethane. The aqueous phase is extracted with ethyl acetate, dried over MgSO4, filtered and concentrated in vacuo. Purification of the residue by silica gel chromatography (dichloromethane-methanol, 1:0 to 99:1 to 49:1 to 97:3) affords 2,6-dimethyl-4-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid ethyl ester as an orange solid. MS (ESI) m/z 399 (M+H)+.

후처리

  1. temperatureto warm to room temperature overnight
  2. customThe mixture is then quenched with saturated aqueous ammonium chloride
  3. additiondiluted with dichloromethane
  4. extractionThe aqueous phase is extracted with ethyl acetate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by silica gel chromatography (dichloromethane-methanol, 1:0 to 99:1 to 49:1 to 97:3)

출처 및 근거

ORD 기록
ord-d838e8654b204580b18299924be62676
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08791141B2

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