1-Chloro-3-iodopropane → Ethyl 4-(3-chloropropyl)-4-cyano-1-piperidinecarboxylate

HRID 1603199Notes

Reaction equation

HRID 1603199 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].C([N-]C(C)C)(C)C.[Li+].[Cl:22][CH2:23][CH2:24][CH2:25]I>O1CCCC1>[Cl:22][CH2:23][CH2:24][CH2:25][C:3]1([C:1]#[N:2])[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 813631-Chloro-3-iodopropaneHCID 2724682Lithium diisopropylamideHCID 4060541Ethyl 4-cyanopiperidine-1-carboxylate

Product 1

HCID 9838044Ethyl 4-(3-chloropropyl)-4-cyano-1-piperidinecarboxylateYield 64.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

To a solution of ethyl 4-cyano-1-piperidinecarboxylate (6.0 g) in tetrahydrofuran (120 ml) at -70° C., under nitrogen, was added a solution of lithium diisopropylamide (4.6 g) in tetrahydrofuran (21.5 ml), dropwise, with stirring. The reaction was allowed to warm to -10° C. and after 30 min was recooled to -70° C. A solution of 1-chloro-3-iodopropane (7.4 g) in tetrahydrofuran (20 ml) was added to the mixture over 30 min. The reaction mixture was quenched with water and allowed to warm to ambient temperature. The mixture was extracted with ethyl acetate. The extracts were washed with water, saturated sodium chloride solution, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was flash chromatographed (silica), eluting with 2:1 heptane/ethyl acetate. The appropriate fractions were collected and concentrated to afford 5.5 g (64%) of product.

Workup

  1. customwas recooled to -70° C
  2. customThe reaction mixture was quenched with water
  3. temperatureto warm to ambient temperature
  4. extractionThe mixture was extracted with ethyl acetate
  5. washThe extracts were washed with water, saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customchromatographed (silica)
  10. washeluting with 2:1 heptane/ethyl acetate
  11. customThe appropriate fractions were collected
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-6a790c4686314a9faaa8626d23390157
Source dataset
uspto-grants-1999_11
Patent number
US05986097

Reaction notes

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