Hydrochloric Acid → HCID 21102203, compound

HRID 2355954Notes

Reaction equation

HRID 2355954 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C:12]#[N:13].[H-].[Na+].C([Li])(CC)C.C1CCCCC1.Cl.[C:28](=O)(O)[O-:29].[Na+]>CN(C)C=O.O1CCCC1>[CH:28]([C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C:12]#[N:13])=[O:29]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8078CyclohexaneHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 21102198HCID 21102198, compoundHCID 178418400CID 53628100

Product 1

HCID 21102203HCID 21102203, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-7-methyl-1H-indole-3-carbonitrile (0.58 g, 2.46 mmol) and sodium hydride (68 mg, 2.7 mmol) were weighed into a flame-dried round-bottom flask containing a magnetic stir bar. Under a nitrogen atmosphere at room temperature, dry tetrahydrofuran (9 mL) was added. The mixture was stirred at room temperature for 15 min, during which time it became homogeneous. The stirred mixture was cooled to −78° C. and a solution of sec-butyllithium in cyclohexane (1.4M, 3.8 mL, 2.2 equiv) was added over several minutes. After 1 h at −78° C., dimethylformamide (0.9 mL) was slowly added and the mixture allowed to warm to room temperature overnight. The solution was cooled to 0° C. and carefully treated with 1N hydrochloric acid. After a few minutes, solid sodium bicarbonate was added until a pH of 9-10 was attained. The two layers were separated and the aqueous phase washed twice with ethyl acetate. The combined organic layers were washed with water (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography gave 60 mg (14%) of desired product and 0.4 g of unreacted starting material. LC/MS: tR=1.21 min, 185.10 (MH)+.

Workup

  1. additioncontaining a magnetic stir bar
  2. temperatureThe stirred mixture was cooled to −78° C.
  3. waitAfter 1 h at −78° C.
  4. temperatureto warm to room temperature overnight
  5. temperatureThe solution was cooled to 0° C.
  6. waitAfter a few minutes
  7. customThe two layers were separated
  8. washthe aqueous phase washed twice with ethyl acetate
  9. washThe combined organic layers were washed with water (2×), brine (2×)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e7e83ac47c4b47128384995f022459ee
Source dataset
uspto-grants-2010_07
Patent number
US07754732B2

Reaction notes

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