Hydrazine hydrate (1:1) → 4-(2-(2-(1-Trityl-1H-imidazol-4-yl)phenoxy)ethyl)aniline

HRID 1023835Notes

Reaction equation

HRID 1023835 reaction equation
[C:1]([N:20]1[CH:24]=[C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[OH:31])[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CC1C=CC(S(O[CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50]([N:53]3C(=O)C4C(=CC=CC=4)C3=O)=[CH:49][CH:48]=2)(=O)=O)=CC=1.O.NN>CN(C=O)C.O>[C:1]([N:20]1[CH:24]=[C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[O:31][CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][C:50]([NH2:53])=[CH:49][CH:48]=2)[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydrideHCID 582940602-(1-trityl-1H-imidazol-4-yl)phenolHCID 866730154-(1,3-Dioxoisoindolin-2-yl)phenethyl 4-methylbenzenesulfonate

Product 1

HCID 672072114-(2-(2-(1-Trityl-1H-imidazol-4-yl)phenoxy)ethyl)anilineYield 60.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of the 2-(1-trityl-1H-imidazol-4-yl)phenol (1.1 g, 2.73 mmol) in DMF (15 mL) was added NaH (83 mg, 3.28 mmol) at 0° C. and the mixture was stirred at room temperature for 1 h. 4-(1,3-dioxoisoindolin-2-yl)phenethyl 4-methylbenzenesulfonate (1.15 g, 2.73 mmol) was added to the mixture. After stirring overnight under a nitrogen atmosphere, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with water (2×20 mL), brine (20 mL) and dried. The solvent was removed under reduced pressure and, the crude product was dissolved in ethanol (15 mL) and treated with hydrazine hydrate (0.3 mL, 5.46 mmol). The mixture was heated at 80° C. for 2 h and filtered. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (silica gel, 30%-50% EtOAc/hexanes as eluent) to afford the desired product as a yellow solid (862 mg, 60% over two steps). 1H NMR: 2.63 (t, 2H, J=7.6 Hz), 4.03 (t, 2H, J=7.6 Hz), 6.46 (d, 1H, J=8.4 Hz), 6.80 (dd, 2H, J=12.4 Hz, 8 Hz), 6.99 (t, 1H, J=7.6 Hz), 7.10-7.19 (m, 7H), 7.28-7.31 (m, 9H), 7.41 (s, 1H), 7.52 (s, 1H), 8.18-8.21 (m, 1H), 8.63 (s, 1H), 9.11 (s, 1H).

Workup

  1. stirringAfter stirring overnight under a nitrogen atmosphere
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. washThe combined organic layers were washed with water (2×20 mL), brine (20 mL)
  4. customdried
  5. customThe solvent was removed under reduced pressure
  6. dissolutionthe crude product was dissolved in ethanol (15 mL)
  7. temperatureThe mixture was heated at 80° C. for 2 h
  8. filtrationfiltered
  9. customThe solvent was removed under reduced pressure
  10. customthe residue was purified by flash column chromatography (silica gel, 30%-50% EtOAc/hexanes as eluent)

Sources & evidence

ORD record
ord-5655af15940f4f659ed29358607853d9
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

Loading…