Trifluoroacetic acid → HCID 22482264, compound

HRID 2181881Notes

Reaction equation

HRID 2181881 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([CH3:16])[N:6]=[C:7]3[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH:3]=1.[BH4-].[Na+].FC(F)(F)C(O)=O.C1C=CC2C3C=CC=CC=3NCC=2C=1.C(N(CC)CC)C.[CH3:47][O:48][C:49]1[CH:54]=[CH:53][C:52]([S:55](Cl)(=[O:57])=[O:56])=[CH:51][CH:50]=1>O1CCCC1.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:6]([S:55]([C:52]1[CH:51]=[CH:50][C:49]([O:48][CH3:47])=[CH:54][CH:53]=1)(=[O:57])=[O:56])[CH:5]2[CH3:16]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 74014-Methoxybenzenesulfonyl chlorideHCID 8471TriethylamineHCID 2199665,6-DihydrophenanthridineHCID 4311764Sodium borohydrideHCID 22482271HCID 22482271, compound

Product 1

HCID 22482264HCID 22482264, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 8-chloro-6-methylphenanthridine (1.6 g, 7.03 mmol) in tetrahydrofuran (67 mL) was treated with sodium borohydride (2.13 g, 56.2 mmol) and trifluoroacetic acid (1.08 mL, 3.51 mmol) and heated at reflux for 5.5 hours. After cooling to room temperature, the reaction was quenched with a mixture of a saturated, aqueous, sodium bicarbonate solution and a saturated, aqueous, sodium chloride solution. The aqueous phase was extracted with diethyl ether (3×). The combined organic phase was dried over anhydrous magnesium sulfate, filtered, and evaporated in vacuo to a crude dihydrophenanthridine. A solution of the dihydrophenanthridine in dichloromethane (19 mL) was treated with triethylamine (3.9 mL, 28.1 mmol) and 4-methoxybenzenesulfonyl chloride (1.60 g, 7.73 mmol). After stirring for 18 hours under argon at room temperature, the reaction mixture was quenched with a 1 N aqueous sodium hydroxide solution, and extracted with dichloromethane (2×). The combined organic phase was washed with a 2 N hydrochloric acid solution, dried over anhydrous magnesium sulfate, and evaporated in vacuo to an orange solid. The orange solid was purified by flash column chromatography on silica gel, eluting with a mixture of ethyl acetate-hexane (1:8) to yield the title compound (1.65 g, 4.11 mmol, 59%) as a white solid;

Workup

  1. temperatureheated
  2. temperatureat reflux for 5.5 hours
  3. customthe reaction was quenched with a mixture of a saturated, aqueous, sodium bicarbonate solution
  4. extractionThe aqueous phase was extracted with diethyl ether (3×)
  5. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo to a crude dihydrophenanthridine
  8. customthe reaction mixture was quenched with a 1 N aqueous sodium hydroxide solution
  9. extractionextracted with dichloromethane (2×)
  10. washThe combined organic phase was washed with a 2 N hydrochloric acid solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customevaporated in vacuo to an orange solid
  13. customThe orange solid was purified by flash column chromatography on silica gel
  14. washeluting with a mixture of ethyl acetate-hexane (1:8)

Sources & evidence

ORD record
ord-4e6f2c5cecf9417780a03a6265a7eff6
Source dataset
uspto-grants-2005_05
Patent number
US06894061B2

Reaction notes

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