Sodium Hydroxide → HCID 68281565, compound

HRID 2278654Notes

Reaction equation

HRID 2278654 reaction equation
C([BH3-])#N.[Na+].[F:5][C:6]([F:18])([F:17])[O:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH:10]=[CH:11][NH:12]2.[OH-].[Na+]>FC(F)(F)C(O)=O.C(OCC)(=O)C>[F:18][C:6]([F:5])([F:17])[O:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][CH2:11][NH:12]2

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 53418161HCID 53418161, compound

Product 1

HCID 68281565HCID 68281565, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

0.57 g of sodium cyanoborohydride is gradually added to a solution of 0.87 g of 4-(trifluoromethoxy)indole in 12 ml of trifluoroacetic acid under argon, cooled to a temperature of about −5° C. The reaction mixture is allowed to warm up to 0° C. for 3 hours, and is then poured into 30 g of ice and alkalinized with 21 ml of a concentrated sodium hydroxide solution. After stirring for 19 hours, the mixture is diluted with 60 ml of ethyl acetate and then stirred at ambient temperature for 30 minutes. After settling out, the organic phase is separated and the aqueous phase is extracted with 3×60 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is treated again with a mixture of 50 ml of water, 50 ml of ethyl acetate and 10 ml of a concentrated sodium hydroxide solution and stirred at ambient temperature for 30 minutes, and then separated by settling out. The organic phase is separated and the aqueous phase is extracted with 3×50 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution being carried out with 95/5; 90/10; then 85/15 v/v cyclohexane/ethyl acetate mixtures, at a flow rate of 25 ml/min. 0.18 g of impure 4-(trifluoromethoxy)indoline is thus obtained in the form of a yellow oil which is directly used in the next step.

Workup

  1. temperatureto warm up to 0° C. for 3 hours
  2. stirringstirred at ambient temperature for 30 minutes
  3. customthe organic phase is separated
  4. extractionthe aqueous phase is extracted with 3×60 ml of ethyl acetate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. additionThe residue is treated again with a mixture of 50 ml of water, 50 ml of ethyl acetate and 10 ml of a concentrated sodium hydroxide solution
  9. stirringstirred at ambient temperature for 30 minutes
  10. customseparated
  11. customThe organic phase is separated
  12. extractionthe aqueous phase is extracted with 3×50 ml of ethyl acetate
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated to dryness under reduced pressure
  16. customThe residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution

Sources & evidence

ORD record
ord-201cfa759e354d3192e1a6e721552f50
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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