Water → HCID 58557552, compound

HRID 1969684Notes

Reaction equation

HRID 1969684 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[C:5]2=[N:6][CH:7]=1.C([Li])(CC)C.Cl[C:27](=[O:42])[CH2:28][CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1.O>C1COCC1>[Cl:1][C:2]1[C:3]([C:27](=[O:42])[CH2:28][CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[CH2:31][CH2:30]2)=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 242292415-Chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridineHCID 57428547HCID 57428547, compoundHCID 178418400CID 53628100

Product 1

HCID 58557552HCID 58557552, compoundYield 25.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (0.338 g, 1.09 mmol, Adesis) in THF (5.5 mL) at about −78° C. was added sec-butyllithium (1.015 mL, 1.421 mmol) drop-wise. The reaction mixture was stirred at about −78° C. for about 1 h then a suspension of tert-butyl 4-(2-chloro-2-oxoethyl)piperidine-1-carboxylate (0.429 g, 1.64 mmol, Preparation #WWWW.1) in THF (2 mL) was added. The reaction mixture was stirred at about −78° C. for about 1 h then allowed to reach ambient temperature. Water (5 mL) was added and the product was extracted into DCM (3×10 mL). The combined organic extracts were washed with brine and dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 0-30% EtOAc in heptane to afford tert-butyl 4-(2-(5-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-2-oxoethyl)piperidine-1-carboxylate (0.147 g, 25%) as a colorless oil: LC/MS (Table 1, Method r) Rt=3.97 min; MS m/z: 534/536 (M+H)+

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at about −78° C. for about 1 h
  3. customto reach ambient temperature
  4. extractionthe product was extracted into DCM (3×10 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by silica gel chromatography
  10. washeluting with 0-30% EtOAc in heptane

Sources & evidence

ORD record
ord-5acd905b78ed4d94982a2113216fb15d
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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