Morpholine → 4-(3-Bromo-4,5-dimethoxyphenyl)-2-hydroxy-7-methyl-pyrrolo[2,3-h]chroman

HRID 1454002Notes

Reaction equation

HRID 1454002 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[CH3:11].[Br:12][C:13]1[CH:14]=[C:15]([CH:23]=[CH:24][CH:25]=[O:26])[CH:16]=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20].N1CCOCC1>CO>[Br:12][C:13]1[CH:14]=[C:15]([CH:23]2[C:10]3[C:2](=[C:3]4[CH:4]=[CH:5][N:6]([CH3:11])[C:7]4=[CH:8][CH:9]=3)[O:1][CH:25]([OH:26])[CH2:24]2)[CH:16]=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 158257394-Hydroxy-1-methylindoleHCID 858878623-(3-Bromo-4,5-dimethoxyphenyl)-propenal

Product 1

HCID 103872724-(3-Bromo-4,5-dimethoxyphenyl)-2-hydroxy-7-methyl-pyrrolo[2,3-h]chromanYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 4-hydroxy-N-methyl indole (11 mg, 0.075 mmol) and 3-(3-bromo-4,5-dimethoxyphenyl)-propenal (20 mg, 0.074 mmol) in methanol (0.6 ml) containing morpholine (7 μl, 0.08 mmol) was held under reflux for 2 h and the mixture was allowed to stir at room temperature overnight. The solvent was evaporated to dryness. The residue was dissolved in acetic acid (0.8 ml) and water was added until the mixture became turbid. It was held at 50° C. for 10 minutes. It was cooled and added slowly to saturated sodium bicarbonate solution. The product was extracted with dichloromethane, washed with saturated sodium chloride solution and dried over sodium sulphate. The solvent was evaporated and the crude product was passed through a bond-elute (hexane:ethyl acetate=9:1 and 8:2 as eluents), giving the title compound (16 mg, 52%). 1H NMR (acetone-d6): 7.09 and 7.08 (d each, J=2.9 Hz; 1H), 7.00 and 6.98 (d each, J=1.7 Hz; 1H), 6.95 and 6.93 (d each, J=1.7 Hz; 1H), 6.85 and 6.83 (d each, J=8.6 Hz; 1H), 6.55 and 6.50 (d each, J=8.5 Hz; 1H), 6.42 and 6.41 (d each, J=3.3 Hz; 1H), 6.15 (fine split doublet, J=6.8 Hz) and 6.08 (d, J=4.9 HZ) (1H), 5.67-5.70 and 5.54-5.58 (m each, 1H), 4.34 (overlapping dd, J=5.8, 10.1 Hz; 1H), 3.84, 3.81, 3.78 and 3.75 (s each, 9H), 2.38-2.43 and 2.09-2.25 (m each, 2H).

Workup

  1. temperatureunder reflux for 2 h
  2. customThe solvent was evaporated to dryness
  3. dissolutionThe residue was dissolved in acetic acid (0.8 ml)
  4. additionwater was added until the mixture
  5. waitIt was held at 50° C. for 10 minutes
  6. temperatureIt was cooled
  7. additionadded slowly to saturated sodium bicarbonate solution
  8. extractionThe product was extracted with dichloromethane
  9. washwashed with saturated sodium chloride solution
  10. dry with materialdried over sodium sulphate
  11. customThe solvent was evaporated
  12. washa bond-elute (hexane:ethyl acetate=9:1 and 8:2 as eluents)

Sources & evidence

ORD record
ord-0a3665e4dbfb4b17bca450c7051a1ff0
Source dataset
uspto-grants-2009_01
Patent number
US07476741B2

Reaction notes

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