Dabco → HCID 68877689, compound

HRID 490207Notes

Reaction equation

HRID 490207 reaction equation
N12CCN(CC1)CC2.C([Li])CCC.[Cl:14][C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.[O:21]=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1>C(OCC)C>[Cl:14][C:15]1[C:16]([C:22]2([OH:21])[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:26][CH2:27]2)=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 9237DabcoHCID 122873-ChloropyridineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 68877689HCID 68877689, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
-50 °C

Procedure

To a solution of 1,4-diazabicyclo[2.2.2]octane (DABCO, 680 mg, 6.06 mmol) in diethyl ether (20 mL) at −78° C. was added n-butyllithium (2.5M in hexanes, 3.0 mL) and stirring continued for 20 minutes. To this mixture was added 3-chloropyridine (700 mg, 6.16 mmol) as a solution in diethyl ether (5 mL). After 30 minutes, tert-butyl 4-oxo-1-piperidinecarboxylate (1.3o g, 6.52 mmol) was added as a solution in diethyl ether (1 mL). The reaction mixture was stirred at −78° C. for 2.5 hours then warmed to −50° C. and quenched with water. The mixture was allowed to warm to room temperature overnight. The layers were separated and the organic phase dried, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (gradient elution with 20% to 99% ethyl acetate:hexanes) to provide the title compound (110 mg, 9% yield). 1H NMR (500 MHz, CDCl3) δ 1.38 (br d, 2H, J=13.7 Hz), 1.50 (s, 9H), 2.73 (ddd, 2H, J=13.1, 13.1, 5.3 Hz), 3.31 (br m, 2H), 4.09 (br m, 2H), 7.25 (m, 1H), 7.74 (dd, 1H, J=7.8, 1.3 Hz), 8.46 (dd, 1H, J=4.7, 1.6 Hz).

Workup

  1. waitAfter 30 minutes
  2. stirringThe reaction mixture was stirred at −78° C. for 2.5 hours
  3. customquenched with water
  4. temperatureto warm to room temperature overnight
  5. customThe layers were separated
  6. customthe organic phase dried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash column chromatography on silica gel (gradient elution with 20% to 99% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-d204ae2bd52b4f3eb00b1d1a7d483dfe
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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