Vinyl chloroformate → 6-Methoxy-8-(4-piperidin-4-ylpiperazin-1-yl)quinoline

HRID 2241989Notes

Reaction equation

HRID 2241989 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:21]=[C:22]([O:30][CH3:31])[CH:23]=[C:24]4[C:29]=3[N:28]=[CH:27][CH:26]=[CH:25]4)[CH2:16][CH2:15]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C(OC(Cl)=O)=C>C(Cl)Cl>[CH3:31][O:30][C:22]1[CH:23]=[C:24]2[C:29](=[C:20]([N:17]3[CH2:16][CH2:15][N:14]([CH:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[CH2:19][CH2:18]3)[CH:21]=1)[N:28]=[CH:27][CH:26]=[CH:25]2

Participants

4

Reactant 2

HCID 78808Vinyl chloroformateHCID 59204845HCID 59204845, compound

Product 1

HCID 592048666-Methoxy-8-(4-piperidin-4-ylpiperazin-1-yl)quinolineYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 8-[4-(1-benzylpiperidin-4-yl)piperazin-1-yl]-6-methoxyquinoline (Step 1, 0.22 g) and vinylchloroformate (0.067 mL) in anhydrous CH2Cl2 (5 mL) was stirred at reflux for 1 hour. The reaction was cooled to room temperature and then concentrated on a rotary evaporator. The residue was taken up in dioxane (5 mL), treated with concentrated HCl (0.35 mL) and stirred at room temperature for 1 hour. The resulting reaction was concentrated on a rotary evaporator, taken up in ethanol (1 mL) and stirred at 50° C. for 30 minutes. The reaction was again concentrated on a rotary evaporator and partitioned between CH2Cl2 and 1N aqueous NaOH. The organic layer was washed with water and then brine and was then dried over anhydrous Na2SO4, filtered and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using ethyl acetate/methanol/conc, NH4OH to give 0.14 g of the desired product as a yellow oil; MS (ES) m/z (relative intensity); 326 (M+H)+ (100).

Workup

  1. temperatureat reflux for 1 hour
  2. concentrationconcentrated on a rotary evaporator
  3. additiontreated with concentrated HCl (0.35 mL)
  4. customThe resulting reaction
  5. concentrationwas concentrated on a rotary evaporator
  6. stirringstirred at 50° C. for 30 minutes
  7. concentrationThe reaction was again concentrated on a rotary evaporator
  8. custompartitioned between CH2Cl2 and 1N aqueous NaOH
  9. washThe organic layer was washed with water
  10. dry with materialbrine and was then dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated on a rotary evaporator
  13. customThe crude product was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-b2c8b299a30342be976c697cb3cba715
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

Loading…