Lithium diisopropylamide → Ethyl 1-azabicyclo(2.2.2)octane-4-carboxylate

HRID 1817212Notes

Reaction equation

HRID 1817212 reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:6][CH2:5]1.[Li+].CC([N-]C(C)C)C>C1COCC1>[N:4]12[CH2:9][CH2:8][C:7]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:6][CH2:5]1)[CH2:2][CH2:3]2

Participants

4

Reactant 2

HCID 2724682Lithium diisopropylamideHCID 61287119Ethyl 1-(2-chloroethyl)piperidine-4-carboxylate

Product 1

HCID 573424Ethyl 1-azabicyclo(2.2.2)octane-4-carboxylateYield 95.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 1-(2-chloroethyl)-4-piperidinecarboxylate (20.42 g, 92.9 mmol) in THF (600 mL) was cooled to −50° C. under Ar. LDA (2.0 M in heptane/THF/ethyl benzene, 70 mL, 140 mmol) was slowly added to the solution at −50° C. over 25 min. The reaction was allowed to warm up to room temperature overnight. The reaction was quenched with K2CO3 (saturated aqueous) (500 mL) and extracted with Et2O (3×500 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The resulting orange oil was co-evaporated three times with CH2Cl2 to remove excess ethyl benzene, resulting in the title compound (16.29 g, 95.7%). EI-MS m/z 184 (M+H+) Rt (1.08 min).

Workup

  1. customThe reaction was quenched with K2CO3 (saturated aqueous) (500 mL)
  2. extractionextracted with Et2O (3×500 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto remove excess ethyl benzene

Sources & evidence

ORD record
ord-cf4b577634a94fa5af17c3055eb53e04
Source dataset
uspto-grants-2009_10
Patent number
US07598267B2

Reaction notes

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