Ethyl chloroformate → HCID 58382073, compound

HRID 1628017Notes

Reaction equation

HRID 1628017 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:3]=12.[Li]C(CC)C.Cl[C:27]([O:29][CH2:30][CH3:31])=[O:28]>C1COCC1>[Cl:1][C:2]1[C:7]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:6][N:5]=[C:4]2[N:8]([Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])[CH:9]=[CH:10][C:3]=12

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 114382724-Chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418400CID 53628100

Product 1

HCID 58382073HCID 58382073, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (0.856 g, 2.77 mmol, Preparation #1, Step A) in THF (20 mL) at about −78° C. was added sec-BuLi (4.35 mL1, 6.10 mmol) dropwise. The reaction was stirred at −78° C. for about 80 min. To the mixture was added ethyl chloroformate (0.665 mL, 6.93 mmol. The flask was removed from the cooling bath and stirred for about 70 min at rt. The mixture was quenched by the addition of a saturated aqueous NH4Cl (5 mL). EtOAc (20 mL) and water (20 mL) were added and the layers were separated. The aqueous layer was extracted with EtOAc (2×15 mL), and the combined organic layers were washed with brine (20 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The material was purified by flash chromatography (40 g Redi-Sep™ silica column) eluting with 0-10% EtOAc in heptane to give ethyl 4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (1.02 g, 97%): 1H NMR (400 MHz, DMSO) δ 8.69 (s, 1H), 7.69 (d, J=3.6, 1H), 6.72 (dd, J=68.4, 3.5, 1H), 4.34 (q, J=7.0, 2H), 1.86 (dt, J=15.0, 7.5, 3H), 1.34 (t, J=7.1, 3H), 1.05 (d, J=7.5, 18H).

Workup

  1. customThe flask was removed from the cooling bath
  2. stirringstirred for about 70 min at rt
  3. customThe mixture was quenched by the addition of a saturated aqueous NH4Cl (5 mL)
  4. additionEtOAc (20 mL) and water (20 mL) were added
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
  7. washthe combined organic layers were washed with brine (20 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe material was purified by flash chromatography (40 g Redi-Sep™ silica column)
  12. washeluting with 0-10% EtOAc in heptane

Sources & evidence

ORD record
ord-411de61ea2024292aa9dd8996eda2926
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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