Dichloromethane → HCID 131732642, compound

HRID 882089Notes

Reaction equation

HRID 882089 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]=[CH:11][CH:10]=[C:9]([C@@H:13]([OH:24])[C@H:14]3[N:19]4[CH2:20][C@H:21]([CH:22]=[CH2:23])[C@@H:16]([CH2:17][CH2:18]4)[CH2:15]3)[C:7]=2[CH:8]=1.C(N(CC)CC)C.ClCCl.[F:35][C:36]([F:42])([F:41])[S:37](Cl)(=[O:39])=[O:38]>C(#N)C.O.C(Cl)(Cl)Cl.CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:12]=[CH:11][CH:10]=[C:9]([C@@H:13]([OH:24])[C@H:14]3[N:19]4[CH2:20][C@H:21]([CH:22]=[CH2:23])[C@@H:16]([CH2:17][CH2:18]4)[CH2:15]3)[C:7]=2[CH:8]=1.[O-:38][S:37]([C:36]([F:42])([F:41])[F:35])(=[O:2])=[O:39]

Participants

8

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 79000Trifluoromethanesulfonyl chlorideHCID 3034034Quinine

Product 1

HCID 131732642HCID 131732642, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

A two-necked flask (internal volume: 30 mL) charged with magnetic stir bars was charged with demethylated quinine (quinine-OH) (465.6 mg, 1.5 mmol). The flask was cooled to 0° C., triethylamine (238 μL, 1.1 equiv.), dichloromethane (3.0 mL), and trifluoromethanesulfonyl chloride (166 μL, 1.05 equiv.) were added to the flask, and the mixture was reacted at room temperature with stirring. After 8 hours, the reaction was quenched by adding a saturated sodium hydrogen carbonate aqueous solution (5 mL) to the reaction mixture, and the reaction mixture was separated into two layers. The organic layer (dichloromethane solution) was isolated preparatively, and 15 mL of dichloromethane was added to the aqueous layer to extract the product. The above operation was repeated four times. An excess amount of anhydrous magnesium sulfate was added to the collected organic layer (dichloromethane solution), and the mixture was filtered. The solvent was evaporated under reduced pressure to obtain a concentrate including a crude product. The concentrate was sequentially subjected to silica gel flash column chromatography (eluant: chloroform/methanol=9/1, Rf=0.26)) and reversed-phase high-performance liquid chromatography (eluant: water and acetonitrile (gradient)) to obtain quinine triflate (white solid, 265.9 mg) (see below). The yield thereof was 40%.

Workup

  1. additionA two-necked flask (internal volume: 30 mL) charged
  2. customthe mixture was reacted at room temperature
  3. stirringwith stirring
  4. customthe reaction was quenched
  5. additionby adding a saturated sodium hydrogen carbonate aqueous solution (5 mL) to the reaction mixture
  6. customthe reaction mixture was separated into two layers
  7. customThe organic layer (dichloromethane solution) was isolated preparatively
  8. extractionto extract the product
  9. additionAn excess amount of anhydrous magnesium sulfate was added to the collected organic layer (dichloromethane solution)
  10. filtrationthe mixture was filtered
  11. customThe solvent was evaporated under reduced pressure
  12. customto obtain a concentrate

Sources & evidence

ORD record
ord-1a93193a5d424b86a2ebf10945413537
Source dataset
uspto-grants-2015_03
Patent number
US08993777B2

Reaction notes

Loading…