Iodine → Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate

HRID 912530Notes

Reaction equation

HRID 912530 reaction equation
II.Br[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:10]([N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C(=O)(O)[O-].[Na+]>C1COCC1.[Zn].C(OCC)(=O)C>[CH2:8]([O:7][C:5](=[O:6])[CH2:4][C:20]1([OH:23])[CH2:19][CH2:18][N:17]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:22][CH2:21]1)[CH3:9]

Participants

8

Reactant 4

HCID 807Iodine2×HCID 7748Ethyl bromoacetateHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 10469302Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylateYield 90.8%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Iodine (12.7 g) was added to the suspension of zinc dust (20 g) in dry THF (200 ml) under nitrogen. An exothermic reaction takes place within 2 minutes and iodine disappeared in less the 10 minutes (a cold water bath is ready to cool the reaction down, but not used). To above mixture was then added by syringe a solution of mixture of ethyl bromoacetate (10.9 g) and N-Boc-4-piperidinone (10 g) in THF (50 ml) on the speed to maintain the reaction at gentle reflux. After stirring for 2 more hours, this mixture was then poured to the mixture of aqueous sodium bicarbonate (200 ml) and ethyl acetate (500 ml). Organic layer was seperated, washed with brine (200 ml), dried over sodium sulphate, solvent removed, the residue was columned on silica gel using heptane:EtOAc (10:1) as eluant to give expected product as a colourless oil (13.1 g). 1H NMR (CDCl3) δ: 4.18 (q, 2H), 3.80 (br, 2H), 3.57 (s, 1H), 3.22 (t, br, 2H), 2.46 (s, 2H), 1.67 (m, 2H), 1.47 (m, 2H), 1.46 (s, 9H), 1.28 (t, 3H).

Workup

  1. customAn exothermic reaction
  2. customwithin 2 minutes
  3. customthe 10 minutes
  4. temperatureto cool
  5. customthe reaction down
  6. additionTo above mixture was then added by syringe
  7. temperatureto maintain
  8. customthe reaction at gentle reflux
  9. customOrganic layer was seperated
  10. washwashed with brine (200 ml)
  11. dry with materialdried over sodium sulphate, solvent
  12. customremoved

Sources & evidence

ORD record
ord-7192103928eb4fa899dcd6e86852083f
Source dataset
uspto-grants-2011_09
Patent number
US08026236B2

Reaction notes

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