Citric Acid → 5-Methyl-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine

HRID 253371Notes

Reaction equation

HRID 253371 reaction equation
Br[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.[CH3:21][Mg]Br.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:21][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

Participants

6

Reactant 3

HCID 311Citric AcidHCID 242292235-Bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418573HCID 178418573, compound

Product 1

HCID 497589615-Methyl-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To PdCl2(dppf) (0.04 g, 0.05 mmol) in toluene (10.0 mL) under an atmosphere of nitrogen were added 5-bromo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (2, 0.3 g, 0.8 mmol, prepared as described in Example 4, 1.0 mL in toluene) and methylmagnesium bromide (1.0 M in tetrahydrofuran, 3.0 mL, 3.0 mmol). The reaction was stirred 90° C. for 2 hours and then allowed to reach to room temperature. The reaction was poured into citric acid (0.1 M in water) and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 50% ethyl acetate in hexane to give the compound (12, 0.16 g 60.0%). MS (ESI) [M+H+]+=289.4.

Workup

  1. customto reach to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified by silica gel column chromatography
  8. washeluting with 50% ethyl acetate in hexane
  9. customto give the compound (12, 0.16 g 60.0%)

Sources & evidence

ORD record
ord-6f8b73e006614e25811762bfe1859ec7
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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