Hydrochloric Acid → HCID 21102202, compound

HRID 1177782Notes

Reaction equation

HRID 1177782 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]#[N:12].[H-].[Na+].C([Li])(CC)C.C1CCCCC1.Cl.[C:27](=O)(O)[O-:28].[Na+]>CN(C)C=O.O1CCCC1>[CH:27]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]#[N:12])=[O:28]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8078CyclohexaneHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 36233545-Bromo-3-cyanoindoleHCID 178418400CID 53628100

Product 1

HCID 21102202HCID 21102202, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-1H-indole-3-carbonitrile (4.25 g, 19.23 mmol) and sodium hydride (0.51 g, 21.2 mmol) were weighed into a flame-dried round-bottom flask containing a magnetic stir bar. Under a nitrogen atmosphere at room temperature, dry tetrahydrofuran (24 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, 30.2 mL, 2.2 equiv) was added over several minutes. After 1 h at −78° C., dimethylformamide (6.0 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 1 N hydrochloric acid (45 mL). 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 2.4 g (72%) of pure material. LC/MS: tR=0.99 min, 171.07 (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-a69675bcd26e4b39b0089f6301567659
Source dataset
uspto-grants-2010_11
Patent number
US07842808B2

Reaction notes

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