Sodium hydride → 2-Methyl-4-{[(piperidin-4-yl)oxy]methyl}quinoline

HRID 1823960Notes

Reaction equation

HRID 1823960 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.[H-].[Na+].[CH3:17][C:18]1[CH:27]=[C:26]([CH2:28]OC2C=CC(CCl)=CC=2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=1>C1COCC1>[CH3:17][C:18]1[CH:27]=[C:26]([CH2:28][O:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 22148916HCID 22148916, compound

Product 1

HCID 221489212-Methyl-4-{[(piperidin-4-yl)oxy]methyl}quinolineYield 15.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To commercially available N-Boc-4-piperidinol (1.00 g, 5.0 mmol) in THF (50 mL) was added NaH (238 mg 60% oil dispersion) and after 25 min, 4-[(2-methyl-4-quinolinyl)methoxy]benzyl chloride (950 mg, 5.00 mmol). After 18 h, the reaction was quenched with water, the THF was removed by rotary evaporator, and the residue was extracted from water with 3×EtOAc. The combined organic extracts were dried over MgSO4, filtered, concentrated, and chromatographed on SiO2 using 40% EtOAc in hexane. Obtained 200 mg (11% yield) of desired product which was treated with TFA (2 mL) in DCM (5 mL) for 1 h. The solvents were removed by rotary evaporator and the product was obtained pure as a free base by extraction from aqueous NaHCO3 with EtOAc after drying over MgSO4, filtering, and concentrating in vacuo. MS found: (M+H)+=257.

Workup

  1. waitAfter 18 h
  2. customthe reaction was quenched with water
  3. customthe THF was removed by rotary evaporator
  4. extractionthe residue was extracted from water with 3×EtOAc
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on SiO2 using 40% EtOAc in hexane

Sources & evidence

ORD record
ord-3f8631b0e69b4c7e9550a6f066ad6aa9
Source dataset
uspto-grants-2006_05
Patent number
US07041693B2

Reaction notes

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