Iodoethane → HCID 58381973, compound

HRID 1628006Notes

Reaction equation

HRID 1628006 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:10](I)=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([CH3:23])[O:22][CH2:21][CH2:20][O:19]4)=[CH:14][CH:13]=3)[N:8]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:5]2=[N:6][CH:7]=1.[Li][CH2:33][CH2:34]CC.C(I)C.[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([CH2:33][CH3:34])=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([CH3:23])[O:22][CH2:21][CH2:20][O:19]4)=[CH:14][CH:13]=3)[N:8]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 25517Ammonium ChlorideHCID 58382134HCID 58382134, compoundHCID 178418339Butyllithium

Product 1

HCID 58381973HCID 58381973, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

2-Bromo-7-iodo-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (17.5 g, 28.4 mmol) in THF (200 mL) was cooled to about −75° C. then n-BuLi (1.6 M in hexanes, 19.5 mL, 31.2 mmol) was added keeping the temperature between about −70 and −75° C. The mixture was stirred for about 5 min at about −75° C. The mixture was treated with EtI (6.2 mL, 77 mmol) then the temperature of the mixture was raised to about 15° C. over about 5 to 10 min. The mixture was stirred at about 20° C. for about 30 min then saturated aqueous NH4Cl (10 mL) was added. The mixture was stirred for about 15 min at about 20° C. then concentrated under reduced pressure. The material was partitioned between Et2O (200 mL) and water (100 mL) the layers were separated and then the aqueous layer was extracted with Et2O (100 mL). The combined organic layers were washed with saturated aqueous NaCl (50 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was applied to a 120 g silica column and eluted with 9:1 heptane/EtOAc. The fractions largely free of impurities were collected. The impure fractions were combined and evaporated then a second 80 g silica column was run on this material with 9:1 heptane/EtOAc as an eluent to give a second lot of material largely free of impurities. The material from the two columns were combined then further purified by flash chromatography on a 220 g silica gel cartridge with a gradient of 0 to 10% EtOAc/heptane to give 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 (7.16 g, 49%): LC/MS (Table 2, Method g) Rt=2.0 min; MS m/z 518 (M+H)+.

Workup

  1. customthe temperature between about −70 and −75° C
  2. temperaturethe temperature of the mixture was raised to about 15° C. over about 5 to 10 min
  3. stirringThe mixture was stirred at about 20° C. for about 30 min
  4. stirringThe mixture was stirred for about 15 min at about 20° C.
  5. concentrationthen concentrated under reduced pressure
  6. customThe material was partitioned between Et2O (200 mL) and water (100 mL) the layers
  7. customwere separated
  8. extractionthe aqueous layer was extracted with Et2O (100 mL)
  9. washThe combined organic layers were washed with saturated aqueous NaCl (50 mL)
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. washeluted with 9:1 heptane/EtOAc
  14. customThe fractions largely free of impurities were collected
  15. customevaporated
  16. customto give a second lot of material largely free of impurities
  17. customThe material from the two columns were combined then further purified by flash chromatography on a 220 g silica gel cartridge with a gradient of 0 to 10% EtOAc/heptane

Sources & evidence

ORD record
ord-1fd8ec1917cb439fb9bd7f7dac0b002c
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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