Bromoacetonitrile → 3-Cyano-2-piperidin-1-yl-propionic acid ethyl ester

HRID 1670823Notes

Reaction equation

HRID 1670823 reaction equation
[N:1]1([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:13]([N-:16]C(C)C)(C)[CH3:14].[Li+].CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.BrCC#N>C1COCC1.C(OCC)(=O)C>[CH2:11]([O:10][C:8](=[O:9])[CH:7]([N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[CH2:14][C:13]#[N:16])[CH3:12]

Participants

7

Reactant 4

HCID 11534BromoacetonitrileHCID 6434661-Piperidineacetic acid, ethyl esterHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 673547353-Cyano-2-piperidin-1-yl-propionic acid ethyl esterYield 27%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

Treat a −78° C. solution of ethyl 1-piperidine acetate (20.0 g, 0.117 mol) in THF (200 mL) with a 2M solution of lithium diisopropylamide in heptane/THF/ethylbenzene (70.1 mL, 0.140 mol) and stir at −78° C. for 20 minutes under N2. Treat the reaction with bromoacetonitrile (21.00 g, 0.175 mol) and stir at −78° C. for 15 minutes. Warm the reaction to room temperature and stir 4 hours. Quench the reaction into saturated ammonium chloride. Dilute the reaction with ethyl acetate and wash with water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 0 to 20% ethyl acetate in hexanes gradient to afford 6.74 g (27%) of the titled product. Rf=0.41 (3/1 hexanes/ethyl acetate). ES MS (m/z): 211 (M+1).

Workup

  1. additionTreat
  2. stirringstir at −78° C. for 15 minutes
  3. temperatureWarm
  4. customthe reaction to room temperature
  5. stirringstir 4 hours
  6. customQuench
  7. customthe reaction into saturated ammonium chloride
  8. additionDilute
  9. washwash with water
  10. dry with materialDry the organic layer (Na2SO4)
  11. customremove the solvent in vacuo
  12. customto afford crude product
  13. custompurify with a 0 to 20% ethyl acetate in hexanes gradient

Sources & evidence

ORD record
ord-f216cdcb3f384a4191fa367d5574b2dd
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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