Sodium hydride → HCID 60060150, compound

HRID 1838308Notes

Reaction equation

HRID 1838308 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]1.[CH2:11]([O:13][C:14](=[O:26])[CH2:15][C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[C:18](Cl)[N:17]=1)[CH3:12].C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O.[OH-].[Na+]>[CH2:11]([O:13][C:14](=[O:26])[CH2:15][C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[C:18]([O:3][CH:4]2[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]2)[N:17]=1)[CH3:12]

Participants

8

Reactant 4

HCID 24758Sodium hydride2×HCID 660484-Piperidinol, 1-methyl-HCID 516892Sodium BicarbonateHCID 60060166HCID 60060166, compound

Product 1

HCID 60060150HCID 60060150, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

Sodium hydride (60%, 1.64 g, 41 mmol) is added to a solution of 4-hydroxy-1-methylpiperidine (4.72 g, 41 mmol) in THF (82 mL) at room temperature. The mixture is stirred for a period of 30 minutes. A solution of (6-chloro-3-nitro-pyridin-2-yl)-acetic acid ethyl ester (5.0 g, 20.5 mmol) in THF (10 mL) is then added. The resulting purple mixture is stirred at room temperature for a period of 70 minutes. An additional portion of NaH (410 mg, 10.3 mmol) is added. The resulting mixture is stirred for a period of 70 minutes at room temperature and a saturated solution of NaHCO3 (30 mL) is then added slowly. The mixture is diluted with EtOAc (100 mL) and 1 N NaOH (aq, 10 mL). The layers are partititioned and the aqueous layer extracted with EtOAc (3×50 mL). The combined organic extracts are washed with H2O (50 mL) and brine (50 mL) and dried over Na2SO4. The mixture is filtered to remove the solids, concentrated, and purified by flash chromatography on silica (gradient elution: 50% EtOAc in hexanes to 2% MeOH/CHCl3 with 0.1% NH4OH to 4% MeOH/CHCl3, with 0.1% NH4OH) to give the title compound as a dark brown oil: 1H NMR (400 MHz, CDCl3) δ 8.34 (d, 1H, J=9.1 Hz), 6.73 (d, 1H, J=9.1 Hz), 4.18 (q, 2H, J=7.1 Hz), 4.17 (s, 2H), 2.70-2.65 (m, 2H), 2.35-2.27 (m, 2H), 2.30 (s, 3H), 2.07-2.00 (m, 2H), 1.89-1.80 (m, 2H), 1.25 (t, 3H, J=7.1 Hz); 13C NMR (100 MHz, CDCl3) δ 169.5, 164.6, 150.6, 139.5, 136.5, 111.3, 72.5, 61.4, 53.0, 46.3, 44.0, 30.9, 14.4; MS (CI) m/z 324.2 (M+1).

Workup

  1. stirringThe resulting purple mixture is stirred at room temperature for a period of 70 minutes
  2. stirringThe resulting mixture is stirred for a period of 70 minutes at room temperature
  3. extractionthe aqueous layer extracted with EtOAc (3×50 mL)
  4. washThe combined organic extracts are washed with H2O (50 mL) and brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationThe mixture is filtered
  7. customto remove the solids
  8. concentrationconcentrated
  9. custompurified by flash chromatography on silica (gradient elution: 50% EtOAc in hexanes to 2% MeOH/CHCl3 with 0.1% NH4OH to 4% MeOH/CHCl3, with 0.1% NH4OH)

Sources & evidence

ORD record
ord-5a6a1adb95224a4aab22d5838cf7bb61
Source dataset
uspto-grants-2004_01
Patent number
US06673811B1

Reaction notes

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