Hydrochloric Acid → 1-[2-(2,3-Dihydro-benzo[b]furan-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine hydrochloride

HRID 963210Notes

Reaction equation

HRID 963210 reaction equation
S(O[CH2:12][CH2:13][CH:14]1[CH2:18][O:17][C:16]2[CH:19]=[CH:20][CH:21]=[CH:22][C:15]1=2)(C1C=CC(C)=CC=1)(=O)=O.[CH3:23][O:24][C:25]1[C:26]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[N:27][CH:28]=[CH:29][CH:30]=1.C([O-])([O-])=O.[K+].[K+].[ClH:43]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>[ClH:43].[O:17]1[CH2:18][CH:14]([CH2:13][CH2:12][N:34]2[CH2:35][CH2:36][N:31]([C:26]3[C:25]([O:24][CH3:23])=[CH:30][CH:29]=[CH:28][N:27]=3)[CH2:32][CH2:33]2)[C:15]2[CH:22]=[CH:21][CH:20]=[CH:19][C:16]1=2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 127904951-(3-Methoxypyridin-2-yl)piperazineHCID 190814952,3-Dihydro-3-benzo[b]furanethanol tosylate

Product 1

HCID 190814471-[2-(2,3-Dihydro-benzo[b]furan-3-yl)ethyl]-4-(3-methoxy-2-pyridinyl)piperazine hydrochlorideYield 39%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 6342AcetonitrileSolvent

Procedure

To CH3CN (100 mL) was added 2,3-dihydro-3-benzo[b]furanethanol tosylate (1.50 g, 4.7 mmol), 1-(3-methoxy-2-pyridinyl)piperazine (0.91 g, 4.7 mmol), anhydrous K2CO3 (1.95 g, 14.1 mmol), KI (0.04 g, 0.24 mmol), and tetra-n-butylammonium hydrogen sulfate (0.08 g, 0.24 mmol). The mixture was heated at reflux under N2 atmosphere for 24 h. The reaction was concentrated in vacuo, several mL of H2O added and the reaction extracted with three portions of CH2Cl2. The combined organic extracts were washed with saturated aqueous NaCl solution, dried with anhydrous K2CO3, filtered, and concentrated in vacuo. Silica gel chromatography (EtOAc) of the concentrate afforded the free base which was treated with ethanolic HCl to yield the title compound (0.85 g, 39%, mp 100°-140° C.)

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under N2 atmosphere for 24 h
  3. concentrationThe reaction was concentrated in vacuo, several mL of H2O
  4. additionadded
  5. extractionthe reaction extracted with three portions of CH2Cl2
  6. washThe combined organic extracts were washed with saturated aqueous NaCl solution
  7. dry with materialdried with anhydrous K2CO3
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customSilica gel chromatography (EtOAc) of the concentrate afforded the free base which

Sources & evidence

ORD record
ord-3a8bb19688334aa482684a4f9e6bcc25
Source dataset
uspto-grants-1998_06
Patent number
US05763444

Reaction notes

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