4-Benzyl-4-piperidinol → Palosuran

HRID 2223709Notes

Reaction equation

HRID 2223709 reaction equation
[OH:1][C:2]1([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Cl[CH2:16][CH2:17][NH:18][C:19]([NH:21][C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=[C:24]([CH3:32])[CH:23]=1)=[O:20].C([O-])(O)=O.[Na+]>C1COCC1.C(Cl)Cl>[CH2:8]([C:2]1([OH:1])[CH2:7][CH2:6][N:5]([CH2:16][CH2:17][NH:18][C:19]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=[C:24]([CH3:32])[CH:23]=2)=[O:20])[CH2:4][CH2:3]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 981524-Benzyl-4-piperidinolHCID 516892Sodium BicarbonateHCID 23443661-(2-Chloroethyl)-3-(2-methylquinolin-4-yl)urea

Product 1

HCID 10173280Palosuran

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 4-hydroxy-4-benzyl-piperidine (380.6 mg, 2 mmol) in dry THF (10 mL) is added 1-(2-chloro-ethyl)-3-(2-methyl-quinolin-4-yl)-urea (263.7 mg, 1 mmol) and solid NaHCO3 (672 mg, 8 mmol). The reaction mixture is stirred at 45° C. for 6 days. The reaction mixture is diluted with CH2Cl2 (100 mL) and washed with sat. Na2CO3 (2×30 mL). The aqueous phase is re-extracted with CH2Cl2 (2×25 mL), the combined organic phases are washed with brine (20 mL), dried (Na2SO4), filtered and evaporated. The residue is purified by preparative HPLC to provide the title compound.

Workup

  1. washwashed with sat. Na2CO3 (2×30 mL)
  2. extractionThe aqueous phase is re-extracted with CH2Cl2 (2×25 mL)
  3. washthe combined organic phases are washed with brine (20 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-a7135f3aee1c4ce9b0a672eb0e1b3c3f
Source dataset
uspto-grants-2008_05
Patent number
US07375227B2

Reaction notes

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