Ethyl 1-(2-chloroethyl)-3-piperidinecarboxylate → Ethyl 1-azabicyclo[3.2.1]octane-5-carboxylate

HRID 415325Notes

Reaction equation

HRID 415325 reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][CH:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:5]1.C(NC(C)C)(C)C.[Li]>O1CCCC1>[N:4]12[CH2:5][C:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:2][CH2:3]1)[CH2:7][CH2:8][CH2:9]2

Participants

4

Reactant 2

HCID 15076314Ethyl 1-(2-chloroethyl)-3-piperidinecarboxylateHCID 45051747Lithium diisopropylamine

Product 1

HCID 15663615Ethyl 1-azabicyclo[3.2.1]octane-5-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 1-(2-chloroethyl)piperidine-3-carboxylate (3.73 g, 17 mmol) in tetrahydrofuran (30 mL) was cooled to −65° C. under nitrogen; lithium diisopropylamine (17 mL, 2 M in tetrahydrofuran) was added slowly to the solution at −65° C. in 25 min. The mixture was allowed to warm up to room temperature and stirred overnight. The reaction was quenched with potassium carbonate and extracted with ether. The combined organic layer were dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting orange oil was co-evaporated with dichloromethane three times. The extracts were combined and concentrated to give the ethyl 1-azabicyclo[3.2.1]octane-5-carboxylate (1.9 g, yield 61%). 1H-NMR (400 MHz, CD3OD) δ: 1.33 (t, 3H), 1.90-2.25 (m, 5H), 2.32-2.47 (m, 1H), 3.20-3.38 (m, 3H), 3.40-3.53 (m, 1H), 3.57-3.80 (m, 2H), 4.20 (q, 2H). LC-MS (ESI) (m/z): 184 (M+1)+.

Workup

  1. customThe reaction was quenched with potassium carbonate
  2. extractionextracted with ether
  3. dry with materialThe combined organic layer were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-33fc02836aae480283a12b4dce2350c9
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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