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

HRID 1927023Notes

Reaction equation

HRID 1927023 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 over 16 h. 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 DCM 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-d795056f6032484181f20253a6fd0778
Source dataset
uspto-grants-2012_05
Patent number
US08183257B2

Reaction notes

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