Allyl bromide → 1-tert-Butyl 4-ethyl 4-(prop-2-en-1-yl)piperidine-1,4-dicarboxylate

HRID 1777340Notes

Reaction equation

HRID 1777340 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3]C.C(NC(C)C)(C)C.[CH2:13]([O:15][C:16]([CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)=[O:17])[CH3:14].C(Br)C=C.[Cl-].[NH4+]>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH2:13]([O:15][C:16]([C:18]1([CH2:3][CH:2]=[CH2:1])[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:20][CH2:19]1)=[O:17])[CH3:14]

Participants

8

Reactant 5

HCID 7841Allyl bromideHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 162182701-tert-Butyl 4-ethyl 4-(prop-2-en-1-yl)piperidine-1,4-dicarboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-70 °C

Procedure

n-Butyllithium (15% solution in n-hexane; 24.5 mL, 0.057 mol) is added to a stirred solution of diisopropyl amine (8.38 mL, 0.059 mol) in tetrahydrofuran (140 mL) at −70° C. under an atmosphere of nitrogen and stirred for 30 minutes. A solution of piperidine-1,4-dicarboxylic acid-1-tert-butyl ester-4-ethyl ester (8.0 g, 0.0311 mol) in tetrahydrofuran (20 mL) is introduced at −70° C. Hexamethyl phosphoramide (15 mL) is added and reaction mixture is allowed to stir till the temperature reaches at −45° C. Reaction mixture again cooled to −70° C., allyl bromide (13.5 mL, 0.155 mol) is added and stirred for 1 hour. Saturated aqueous solution of ammonium chloride (100 mL) is added slowly into the reaction mixture at −30° C. and stirred for 10 minutes. It is extracted with ethyl acetate (3×60 mL). Combined organic layer is washed with brine solution (1×30 mL) and dried over sodium sulfate. Removal of solvent under reduced pressure gives a viscous liquid which is purified by column chromatography (silica gel 230-400, n-hexane:ethyl acetate, 9:1) to furnish 4-allyl piperidine-1,4-dicarboxylic acid-1-tert-butylester-4-ethyl ester.

Workup

  1. customreaction mixture
  2. stirringto stir till the temperature
  3. customreaches at −45° C
  4. customReaction mixture
  5. stirringstirred for 1 hour
  6. stirringstirred for 10 minutes
  7. extractionIt is extracted with ethyl acetate (3×60 mL)
  8. washCombined organic layer is washed with brine solution (1×30 mL)
  9. dry with materialdried over sodium sulfate
  10. customRemoval of solvent under reduced pressure
  11. customgives a viscous liquid which
  12. customis purified by column chromatography (silica gel 230-400, n-hexane:ethyl acetate, 9:1)

Sources & evidence

ORD record
ord-6d439d4bc948461991413004e64ec58c
Source dataset
uspto-grants-2016_02
Patent number
US09266867B2

Reaction notes

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