Tert-butyl 3-oxopiperidine-1-carboxylate → 3-Methylene-piperidine-1-carboxylic acid tert-butyl ester

HRID 1852567Notes

Reaction equation

HRID 1852567 reaction equation
[I-].C1([C:8]([PH3+])([C:15]2[CH:20]=C[CH:18]=[CH:17][CH:16]=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])(C)(C)C.[K+].[C:28]([N:35]1CCCC(=O)C1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>C1(C)C=CC=CC=1>[C:28]([N:35]1[CH2:18][CH2:17][CH2:16][C:15](=[CH2:20])[CH2:8]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]

Participants

5

Reactant 3

HCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 66599960Tritylphosphanium iodide

Product 1

HCID 112525943-Methylene-piperidine-1-carboxylic acid tert-butyl esterYield 70.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Triphenylmethyl phosphonium iodide (22.14 g) and toluene (135 ml) are added into a three mouth flask (500 ml), stirred at room temperature to obtain a milky white suspension and quickly changed to orange after potassium tert-butanolate (5.31 g) is added. Then N-Boc-3-piperidone (6.0 g) in toluene (66 ml) is added into a constant pressure funnel and dropped into the flask under argon with obvious exothermic phenomenon, and kept at the temperature of 30° C. and the reaction is tracked by TLC after addition. After reaction, the mixture is filtered and washed with a saturated brine (200 ml, 2 times) and then adjusted to pH≈3 with diluted HCl (1M), and then washed with a saturated brine to pH=7, dried with anhydrous sodium sulfate, and filtered to obtain a yellow transparent liquid. The yellow transparent liquid is purified together with silica gel by chromatography (elution liquid: petroleum ether:ethyl acetate=15:1) to obtain a yellow oil-liquid of N-Boc-3-methylene piperidine (4.2 g).

Workup

  1. customto obtain a milky white suspension
  2. additionis added
  3. additiondropped into the flask under argon with obvious exothermic phenomenon
  4. customkept at the temperature of 30° C.
  5. additionafter addition
  6. customAfter reaction
  7. filtrationthe mixture is filtered
  8. washwashed with a saturated brine (200 ml, 2 times)
  9. washwashed with a saturated brine to pH=7
  10. dry with materialdried with anhydrous sodium sulfate
  11. filtrationfiltered
  12. customto obtain a yellow transparent liquid
  13. customThe yellow transparent liquid is purified together with silica gel by chromatography (elution liquid: petroleum ether:ethyl acetate=15:1)

Sources & evidence

ORD record
ord-a70e17f83fd94856a1395647b3d969fc
Source dataset
uspto-grants-2015_02
Patent number
US08962626B2

Reaction notes

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