4-Methoxybenzenesulfonyl chloride → 5-[(4-Methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine

HRID 2181784Notes

Reaction equation

HRID 2181784 reaction equation
[CH:1]1[C:14]2[C:5](=[N:6][CH:7]=[C:8]3[C:13]=2[CH:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=[CH:3][CH:2]=1.[CH3:15][Li].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=1.[OH-].[Na+]>C(OCC)C>[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([N:6]2[CH:7]([CH3:15])[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]2=3)(=[O:27])=[O:26])=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 9189PhenanthridineHCID 14798Sodium HydroxideHCID 178418348HCID 178418348, compound

Product 1

HCID 224823645-[(4-Methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridineYield 28%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A stirred solution of phenanthridine (3.58 g, 20 mmol) in anhydrous diethyl ether (20 mL) was cooled to −30° C. and treated drop-wise under nitrogen via syringe with a solution of 1.4 M methyllithium in diethyl ether (14.5 mL, 20.3 mmol). The yellow solution was warmed to room temperature and stirred for 15 minutes. The mixture was cooled to −78° C. and treated with 4-methoxybenzenesulfonyl chloride (4.12 g, 20 mmol), as a solid, in a single aliquot. The reaction mixture was warmed slowly to room temperature over one hour, poured into 1 N aqueous sodium hydroxide, and extracted with ethyl acetate. The organic phase was washed sequentially with water, a 1 N hydrochloric acid solution, and a saturated, aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the organic phase was filtered through a short column of silica gel, and the filtrate evaporated in vacuo to yield a crude yellow oil (5.3 g, 73%). The crude oil was purified by preparative chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g), eluting with a mixture of methyl tert-butyl ether-hexane (15:85) at a flow rate of 40 mL/min to afford, after evaporation of the solvent, a colorless oil. Crystallization of the colorless oil from a mixture of diethyl ether-hexane yielded the title compound (2.02 g, 5.6 mmol, 28%) as a homogeneous, colorless, crystalline solid, m.p. 167-169° C.;

Workup

  1. temperatureThe mixture was cooled to −78° C.
  2. temperatureThe reaction mixture was warmed slowly to room temperature over one hour
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed sequentially with water
  5. dry with materialAfter drying over anhydrous sodium sulfate
  6. filtrationthe organic phase was filtered through a short column of silica gel
  7. customthe filtrate evaporated in vacuo
  8. customto yield a crude yellow oil (5.3 g, 73%)
  9. customThe crude oil was purified by preparative chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g)
  10. washeluting with a mixture of methyl tert-butyl ether-hexane (15:85) at a flow rate of 40 mL/min
  11. customto afford
  12. customafter evaporation of the solvent
  13. customCrystallization of the colorless oil
  14. additionfrom a mixture of diethyl ether-hexane

Sources & evidence

ORD record
ord-f5e18fe7817c44d89b4aa65bd7f070ec
Source dataset
uspto-grants-2005_05
Patent number
US06894061B2

Reaction notes

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