1-(Naphthalen-2-yl)piperazine → (2S)-8-methyl-2-{[4-(2-naphthyl)piperazin-1-yl]methyl}-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

HRID 860008Notes

Reaction equation

HRID 860008 reaction equation
BrC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)(=O)=O)=CC=1.[CH:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][C:29]=1[N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>CS(C)=O.C(=O)(O)[O-].[Na+]>[CH3:26][C:21]1[CH:20]=[CH:19][C:18]2[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14][C@H:13]([CH2:12][N:41]4[CH2:40][CH2:39][N:38]([C:29]5[CH:30]=[CH:31][C:32]6[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=6)[CH:28]=5)[CH2:43][CH2:42]4)[O:27][C:17]3=2)[N:22]=1

Participants

5

Reactant 2

HCID 27601721-(Naphthalen-2-yl)piperazineHCID 20624762[(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonate

Product 1

HCID 69605028(2S)-8-methyl-2-{[4-(2-naphthyl)piperazin-1-yl]methyl}-2,3-dihydro[1,4]dioxino[2,3-f]quinolineYield 69.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl 4-bromobenzenesulfonate (2.73 g, 6.06 mmol) and 1-naphthalen-2-yl-piperazine (3.86 g, 18.2 mmol) in anhydrous dimethylsulfoxide (60 mL) was heated at 50° C. overnight. The cooled reaction was diluted with saturated aqueous sodium bicarbonate (200 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were washed with brine (300 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography on silica gel (2/2/95 methanol/ammonium hydroxide/methylene chloride) did not provide clean product. Re-chromatography on silica gel (90/5/5 ethyl acetate/hexane/triethylamine) afforded 1.80 g (69%) of the title compound as a beige solid: mg 134–137° C.; MS (ES) m/z426 [M+H]+.

Workup

  1. customThe cooled reaction
  2. extractionextracted with ethyl acetate (3×200 mL)
  3. washThe combined organic layers were washed with brine (300 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customFlash chromatography on silica gel (2/2/95 methanol/ammonium hydroxide/methylene chloride) did not provide clean product

Sources & evidence

ORD record
ord-aec0a631bb9442f6b01263d17c98c87e
Source dataset
uspto-grants-2006_12
Patent number
US07153849B2

Reaction notes

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