Water → HCID 10354244, compound

HRID 1900395Notes

Reaction equation

HRID 1900395 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[OH:14])[NH:10][CH:9]=[CH:8]2.Br[CH2:16][CH2:17][CH2:18][Cl:19].O>CN(C)C=O>[Cl:19][CH2:18][CH2:17][CH2:16][O:14][C:13]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][C:5]=1[O:4][CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 1270896-Hydroxy-5-methoxyindole

Product 1

HCID 10354244HCID 10354244, compoundYield 108.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
-5 °C

Procedure

To a stirred suspension of sodium hydride (0.94 g, 19.6 mmol of a 50% oil dispersion) in dimethylformamide (20 ml) under nitrogen and cooled to -5° C. was added, dropwise, 5-methoxy-6-hydroxyindole (3.2 g, 19.6 mmol) dissolved in dimethylformamide (60 ml) so that the temperature did not exceed -2° C. After complete addition, the reaction was stirred for 45 minutes at 0° C. While maintaining the reaction temperature between -5° C. and 0° C., a solution of 1-bromo-3-chloropropane (3.1 g, 19.6 mmol) dissolved in dimethylformamide (15 ml) was slowly added. The mixture was stirred at ambient temperature under nitrogen for 21 hours. The reaction was cooled in an ice bath, and water was added to destroy the excess sodium hydride, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water, dried with MgSO4 and concentrated to yield 5.3 g of a dark, oily liquid. This was combined with an additional sample, for a total of 10.0 g, and purification by preparative HPLC (Waters Associates prep LC/System 500) provided 5.1 g of a brown solid. A 2.5 g sample was recrystallized from isopropyl alcohol to yield 1.1 g (30%) of 6-(3-chloropropoxy)o5-methoxyindole as beige crystals, m.p.=73°-75° C.

Workup

  1. additionwas added
  2. customdid not exceed -2° C
  3. additionAfter complete addition
  4. temperatureWhile maintaining the reaction temperature between -5° C. and 0° C.
  5. additionwas slowly added
  6. stirringThe mixture was stirred at ambient temperature under nitrogen for 21 hours
  7. temperatureThe reaction was cooled in an ice bath
  8. customto destroy the excess sodium hydride
  9. extractionthe aqueous mixture was extracted with ethyl acetate
  10. extractionThe ethyl acetate extract
  11. washwas washed with water
  12. dry with materialdried with MgSO4
  13. concentrationconcentrated
  14. customto yield 5.3 g of a dark, oily liquid
  15. customThis was combined with an additional sample, for a total of 10.0 g, and purification by preparative HPLC (Waters Associates prep LC/System 500)

Sources & evidence

ORD record
ord-89558ecb07ad4c83aa2a05b60dc5b1e1
Source dataset
uspto-grants-1996_11
Patent number
US05574032

Reaction notes

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