Hydrochloric Acid → [3-Hydroxy-5-(1H-indol-4-YL)-phenyl]-(6-hydroxymethyl-pyridin-3-YL)-methanone

HRID 1784819Notes

Reaction equation

HRID 1784819 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:18]([C:20]2[CH:21]=[N:22][C:23]([CH3:26])=[CH:24][CH:25]=2)=[O:19])[CH:5]=[C:6]([O:8]CC2C=CC(OC)=CC=2)[CH:7]=1.[Li][CH2:28][CH2:29][CH2:30][CH3:31].CCCCCC.BrC1C=C([O:45]CC2C=CC(OC)=CC=2)C=C(Br)C=1.C[C:57]1[CH:64]=[CH:63][C:60](C#N)=C[N:58]=1.Cl.[OH-].[Na+]>CCOCC>[OH:8][C:6]1[CH:5]=[C:4]([C:18]([C:20]2[CH:21]=[N:22][C:23]([CH2:26][OH:45])=[CH:24][CH:25]=2)=[O:19])[CH:3]=[C:2]([C:28]2[CH:60]=[CH:63][CH:64]=[C:57]3[C:29]=2[CH:30]=[CH:31][NH:58]3)[CH:7]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 8058HexaneHCID 14798Sodium HydroxideHCID 2819956-Methylpyridine-3-carbonitrileHCID 252583101,3-Dibromo-5-[(4-methoxyphenyl)methoxy]benzeneHCID 68846719[3-Bromo-5-(4-methoxy-benzyloxy)-phenyl]-(6-methyl-pyridin-3-yl)-methanoneHCID 178418339Butyllithium

Product 1

HCID 15604424[3-Hydroxy-5-(1H-indol-4-YL)-phenyl]-(6-hydroxymethyl-pyridin-3-YL)-methanoneYield 90%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

[3-Bromo-5-(4-methoxy-benzyloxy)-phenyl]-(6-methyl-pyridin-3-yl)-methanone. A 1.6 M solution of n-BuLi in hexane (1.8 mmol) was added dropwise to a stirred mixture of 1,3-dibromo-5-(4-methoxy-benzyloxy)-benzene (600 mg, 1.6 mmol) in dry ether (6 mL) at −78° C. The resulting solution was stirred at −78° C. for 30 min, and then 6-methyl-nicotinonitrile (190 mg, 1.6 mmol) in dry ether (4 mL) was added dropwise. The mixture was stirred at −78° C. for 1 h, and then the temperature was allowed to rise to 0° C. 2N HCl was added with stirring. The aqueous was then basified with 1N NaOH solution and extracted with methylene chloride three times. The combined organic phase was washed with brine, dried, and concentrated to afford the crude product which was further purified by flash chromatography (3:1 hexane/EtOAc) to yield the desired product as a yellow oil (600 mg, 90%).

Workup

  1. stirringThe mixture was stirred at −78° C. for 1 h
  2. customto rise to 0° C
  3. stirringwith stirring
  4. extractionextracted with methylene chloride three times
  5. washThe combined organic phase was washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customto afford the crude product which
  9. customwas further purified by flash chromatography (3:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-2bf35fd8a86c4627a60c8cc3d7fda835
Source dataset
uspto-grants-2009_03
Patent number
US07504401B2

Reaction notes

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