Piperidine → HCID 86599848, compound

HRID 2099027Notes

Reaction equation

HRID 2099027 reaction equation
O1CCCCC1[O:7][CH2:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[C:19](O)[CH:20]=[CH:21][CH:22]=2)[CH2:13][CH2:12]1.O=P(Cl)(Cl)Cl.N1CCCCC1.[CH3:35][O:36][C:37](=[O:48])[CH2:38][C:39]1[S:40][C:41]2[CH:47]=[CH:46][CH:45]=[CH:44][C:42]=2[N:43]=1>CN(C=O)C.C1(C)C=CC=CC=1>[S:40]1[C:41]2[CH:47]=[CH:46][CH:45]=[CH:44][C:42]=2[N:43]=[C:39]1[C:38]1[C:37](=[O:48])[O:36][C:35]2[C:20]([CH:19]=1)=[CH:21][CH:22]=[C:17]([N:14]1[CH2:13][CH2:12][N:11]([CH2:10][CH2:9][CH2:8][OH:7])[CH2:16][CH2:15]1)[CH:18]=2

Participants

7

Reactant 4

HCID 8082PiperidineHCID 24813Phosphorus oxychlorideHCID 358756Methyl (1,3-benzothiazol-2-yl)acetateHCID 69072933HCID 69072933, compound

Product 1

HCID 86599848HCID 86599848, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

320 mg (1 mmol) 3-{4-[3-(tetrahydro-pyran-2-yloxy)-propyl]-piperazin-1-yl}-phenol is dissolved in 10 mL DMF and treated below 10° C. with 0.1 mL POCl3. The reaction mixture is stirred at room temperature for 6 hours, then evaporated and the crude product taken up in 10 mL acetonitrile and treated with 0.6 mL (6 eq.) piperidine. 207 mg benzothiazol-2-yl-acetic acid methyl ester in 10 mL toluene are added and the reaction mixture stirred for 30 minutes at 90° C. before being evaporated. The residue is taken up in 20 mL anhydrous THF, stirred for two hours in the presence of 1 mL of a 6N aqueous HCl solution and evaporated. The residue is taken up in dichloromethane and washed with aqueous sodium bicarbonate and saline. The organic phase is evaporated and the residue column chromatographed (silica gel, dichloromethane/EtOH/aq. NH3 90:9.9:0.1) to yield 70 mg (17%) desired product as a yellow-orange powder.

Workup

  1. customevaporated
  2. stirringthe reaction mixture stirred for 30 minutes at 90° C.
  3. custombefore being evaporated
  4. stirringstirred for two hours in the presence of 1 mL of a 6N aqueous HCl solution
  5. customevaporated
  6. washwashed with aqueous sodium bicarbonate and saline
  7. customThe organic phase is evaporated
  8. customthe residue column chromatographed (silica gel, dichloromethane/EtOH/aq. NH3 90:9.9:0.1)

Sources & evidence

ORD record
ord-9a75f0c484d7480ea10834a486bce79d
Source dataset
uspto-grants-2009_08
Patent number
US07569337B2

Reaction notes

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