1-Bromopentane → HCID 22497215, compound

HRID 1816130Notes

Reaction equation

HRID 1816130 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])C(F)(F)F)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].[OH-:29].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:16])=[O:29])=[CH:7][N:8]2[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 80571-BromopentaneHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 224972521-(6-Chloro-3-indolyl)-2,2,2-trifluoroethanone

Product 1

HCID 22497215HCID 22497215, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (300 mg, 1.21 mmol), potassium carbonate (419 mg, 3.03 mmol), and 1-bromopentane (0.23 mL, 1.82 mmol) in N,N-dimethylformamide (4 mL) in a sealed reaction vessel was heated at 60° C. for 16 h. At this time, the reaction was cooled to 25° C. and partitioned between water (30 mL) and ethyl acetate (30 mL). This mixture was treated with a 1N aqueous hydrochloric acid solution (6 mL), shaken, and separated. The organic layer was concentrated in vacuo to afford a yellow solid. The resulting solid was treated with a 20% aqueous sodium hydroxide solution (7 mL) and was heated at 115° C. for 24 h. At this time, the reaction was cooled to 25° C. and was partitioned between water (75 mL) and ethyl acetate (75 mL). This solution was treated with a 1N aqueous hydrochloric acid solution (25 mL), shaken, and separated. The organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 6-chloro-1-pentyl-1H-indole-3-carboxylic acid (315 mg, 98%) as a yellow solid: mp 152-154° C.; EI-HRMS m/e calcd for C14H16ClNO2 (M+) 265.0870, found 265.0865.

Workup

  1. customin a sealed reaction vessel
  2. temperatureAt this time, the reaction was cooled to 25° C.
  3. custompartitioned between water (30 mL) and ethyl acetate (30 mL)
  4. additionThis mixture was treated with a 1N aqueous hydrochloric acid solution (6 mL)
  5. customseparated
  6. concentrationThe organic layer was concentrated in vacuo
  7. customto afford a yellow solid
  8. temperaturewas heated at 115° C. for 24 h
  9. temperatureAt this time, the reaction was cooled to 25° C.
  10. customwas partitioned between water (75 mL) and ethyl acetate (75 mL)
  11. additionThis solution was treated with a 1N aqueous hydrochloric acid solution (25 mL)
  12. stirringshaken
  13. customseparated
  14. washThe organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL)
  15. dry with materialdried over magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6f0981a0c009414382c3fbb033799607
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

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