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

HRID 1854484Notes

Reaction equation

HRID 1854484 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][CH:37]([CH:40]=[O:41])[CH2:36][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][CH:37]([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])[CH2:36][CH2:35]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 895841-Benzylpiperidine-4-carbaldehydeHCID 467363645-Chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 58010011(1-benzylpiperidin-4-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)methanolYield 99.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-BuLi (1.6 M in hexanes, 5.17 mL, 8.28 mmol) was added dropwise to a solution of 5-chloro-4-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (3.0 g, 6.9 mmol, Adesis) in THF (120 mL) at about −78° C., keeping the internal temperature of the reaction below about −70° C. during the addition. After stirring for about 40 min, 1-benzylpiperidine-4-carbaldehyde (2.1 g, 10.3 mmol) was added dropwise and the resulting mixture was stirred at about −75° C. for about 1 h. The reaction was quenched by the dropwise addition of saturated aqueous ammonium chloride (60 mL). The mixture was concentrated under reduced pressure and the remaining aqueous portion was extracted with EtOAc (125 mL). The organic layer was washed with brine (80 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure to afford crude (1-benzylpiperidin-4-yl)(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-4-yl)methanol (3.53 g, quantitative) as a yellow oil: LC/MS (Table 2, Method n) Rt=1.82 min; MS m/z: 512 and 514 (M+H)+. The crude material was used directly in the next step without further purification.

Workup

  1. customthe internal temperature of the reaction below about −70° C.
  2. additionduring the addition
  3. stirringthe resulting mixture was stirred at about −75° C. for about 1 h
  4. customThe reaction was quenched by the dropwise addition of saturated aqueous ammonium chloride (60 mL)
  5. concentrationThe mixture was concentrated under reduced pressure
  6. extractionthe remaining aqueous portion was extracted with EtOAc (125 mL)
  7. washThe organic layer was washed with brine (80 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a8bb9dc0cf794a4fa559af91195d5e05
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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