Sodium hydride → 5-(tert-butoxycarbonylmethoxy)-3-(1-naphthoyl)-N-pentyl-1H-indole

HRID 55927Notes

Reaction equation

HRID 55927 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:8]=[C:7]2[C:18]([C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1)=[O:19].Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]>CN(C=O)C>[C:35]([O:34][C:32]([CH2:31][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:8]=[C:7]2[C:18]([C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1)=[O:19])=[O:33])([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 53394447JWH 018 5-hydroxyindole metabolite

Product 1

HCID 681592445-(tert-butoxycarbonylmethoxy)-3-(1-naphthoyl)-N-pentyl-1H-indoleYield 185.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium hydride (452 mg, 13 4 mmol, 60% in mineral oil) in DMF (25 ml) under nitrogen was added dropwise a solution of 6 (3.7 g, 10.35 mmol) in DMF (50 ml) and the mixture was stirred at 60° C. for 1 h. The solution was then cooled to room temperature and to this mixture was added a solution of tert-butyl bromoacetate (2.62 g, 13 4 mmol) in DMF (25 ml). The mixture was stirred at 60° C. for 3 h. The DMF was removed under high vacuum and the crude product was suspended in water (100 ml) and the mixture was extracted by ethyl acetate (2×100 ml). The combined ethyl acetate phases were washed by water (1×50 ml), brine (1×50 ml), dried over sodium sulphate filtered and concentrated to dryness. The crude product obtained was purified by chromatography on silica gel using hexane/ethyl acetate (9/1) to give the title compound 7 (3.5 g, 72%).

Workup

  1. temperatureThe solution was then cooled to room temperature and to this mixture
  2. stirringThe mixture was stirred at 60° C. for 3 h
  3. customThe DMF was removed under high vacuum
  4. extractionthe mixture was extracted by ethyl acetate (2×100 ml)
  5. washThe combined ethyl acetate phases were washed by water (1×50 ml), brine (1×50 ml)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product obtained
  10. customwas purified by chromatography on silica gel

Sources & evidence

ORD record
ord-01756a16bd084dfd81be9ec2f9121fdb
Source dataset
uspto-grants-2016_09
Patent number
US09434687B2

Reaction notes

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