1-Benzylpiperidine-3-carbaldehyde → (1-benzylpiperidin-3-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)methanol

HRID 2204641노트

반응식

HRID 2204641 반응식
[Li]CCCC.[Cl:6][C:7]1[C:8](I)=[C:9]2[CH:15]=[CH:14][N:13]([Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[C:10]2=[N:11][CH:12]=1.[CH2:27]([N:34]1[CH2:39][CH2:38][CH2:37][CH:36]([CH:40]=[O:41])[CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C1COCC1>[CH2:27]([N:34]1[CH2:39][CH2:38][CH2:37][CH:36]([CH:40]([C:8]2[C:7]([Cl:6])=[CH:12][N:11]=[C:10]3[N:13]([Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[CH:14]=[CH:15][C:9]=23)[OH:41])[CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

참가 물질

5

반응물 3

HCID 104428791-Benzylpiperidine-3-carbaldehydeHCID 467363645-Chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

생성물 1

HCID 58010130(1-benzylpiperidin-3-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)methanol수율 99.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of n-BuLi (1.6 N in heptane, 8.62 mL, 13.8 mmol) was added dropwise to a solution of 5-chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (5.00 g, 11.5 mmol, Adesis) in THF (135 mL) at about −78° C., keeping the temperature below about −70° C. After stirring for about 40 min, a solution of 1-benzylpiperidine-3-carbaldehyde (4.21 g, 20.7 mmol) in THF (15 mL) was added dropwise and the resulting mixture was stirred at about −75° C. for about 2 h. The reaction was quenched by dropwise addition of saturated aqueous NH4Cl (100 mL) and the THF was removed under reduced pressure. The aqueous phase was extracted into EtOAc (250 mL), washed with brine (200 mL), and concentrated to yield crude (1-benzylpiperidin-3-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)methanol (5.88 g, quantitative) as a yellow oil that was used directly in the next step without further purification: LC/MS (Table 2, Method a) Rt=1.78 min; MS m/z: 512 and 514 (M+H)+

후처리

  1. customthe temperature below about −70° C
  2. stirringthe resulting mixture was stirred at about −75° C. for about 2 h
  3. customThe reaction was quenched by dropwise addition of saturated aqueous NH4Cl (100 mL)
  4. customthe THF was removed under reduced pressure
  5. extractionThe aqueous phase was extracted into EtOAc (250 mL)
  6. washwashed with brine (200 mL)
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-1a8d98985f2f40b1a62ea4970ef63390
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365579B2

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