Allyl bromide → HCID 58382309, compound

HRID 1628024Notes

Reaction equation

HRID 1628024 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([CH2:11][CH3:12])=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([CH3:24])[O:23][CH2:22][CH2:21][O:20]4)=[CH:15][CH:14]=3)[N:8]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:5]2=[N:6][CH:7]=1.[Li][CH2:34][CH2:35][CH2:36]C.C([Cu])#N.C(Br)C=C.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O.O>[CH2:36]([C:2]1[N:3]=[C:4]2[C:10]([CH2:11][CH3:12])=[C:9]([C:13]3[CH:14]=[CH:15][C:16]([C:19]4([CH3:24])[O:20][CH2:21][CH2:22][O:23]4)=[CH:17][CH:18]=3)[N:8]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:32])[CH3:31])[C:5]2=[N:6][CH:7]=1)[CH:35]=[CH2:34]

Participants

9

Reactant 5

HCID 7841Allyl bromideHCID 516892Sodium BicarbonateHCID 58381973HCID 58381973, compoundHCID 178418339ButyllithiumHCID 178418546HCID 178418546, compound

Product 1

HCID 58382309HCID 58382309, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

2-Bromo-7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.500 g, 0.964 mmol, Preparation #5) in THF (6 mL) was cooled to about −75° C. then the n-BuLi (2.4 M in hexanes, 0.482 mL, 1.16 mmol) was added dropwise. After about 10 min CuCN (0.009 g, 0.010 mmol) was added followed by allyl bromide (0.250 mL, 2.89 mmol). The mixture was stirred at about −70° C. for about 30 min warmed to about −40° C. the mixture was treated with about 2 mL of saturated aqueous NaHCO3 then warmed to rt. The mixture was diluted with EtOAc (20 mL) and water (10 mL). The layers were separated and the aqueous layer extracted with EtOAc (10 mL). The combined organics were washed with brine (10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The material was purified on a 10 gram silica column with 9:1 DCM/EtOAc as an eluent to give 2-allyl-7-ethyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.323 g, 70%): LC/MS (Table 2, Method b) Rt=3.53 min; MS m/z 480 (M+H)+.

Workup

  1. temperaturewarmed to about −40° C. the mixture
  2. temperaturethen warmed to rt
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with EtOAc (10 mL)
  5. washThe combined organics were washed with brine (10 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe material was purified on a 10 gram silica column with 9:1 DCM/EtOAc as an eluent

Sources & evidence

ORD record
ord-f64285ea8b5e49b5be4af30b184fb362
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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