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

HRID 2204641Notes

Reaction equation

HRID 2204641 reaction equation
[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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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)+

Workup

  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

Sources & evidence

ORD record
ord-1a8d98985f2f40b1a62ea4970ef63390
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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