Methyl iodide → 1-(2,3-Dihydrobenzo[1,4]dioxin-2-ylmethyl)-3-methylpiperidine-3-carboxylic acid ethyl ester

HRID 453775Notes

Reaction equation

HRID 453775 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][CH:13]2[O:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)[CH2:7]1)=[O:5])[CH3:2].[Li+].[CH3:24]C([N-]C(C)C)C.CI>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1([CH3:24])[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][CH:13]2[O:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[O:15][CH2:14]2)[CH2:7]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 251754981-(2,3-Dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidine-3-carboxylic acid ethyl ester

Product 1

HCID 251755001-(2,3-Dihydrobenzo[1,4]dioxin-2-ylmethyl)-3-methylpiperidine-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidine-3-carboxylic acid ethyl ester (10.05 g, 32.90 mmol) in dry THF (100 ml) at −78° C. was slowly added LDA (20.1 ml, 1.8 M). The reaction mixture was stirred at this temperature for 1 h. Methyl iodide (2.25 ml, 36.21 mmol) was then added, the cooling bath removed and stirring was continued for 10 h. After addition of water, the reaction mixture was extracted with EtOAc (3×25 ml). The combined organic phases were dried over Na2SO4, filtered and the filtrate was evaporated to give the title compound, which was purified by column chromatography (EtOAc/heptane, 70:30).

Workup

  1. customat −78° C.
  2. customthe cooling bath removed
  3. stirringstirring
  4. waitwas continued for 10 h
  5. additionAfter addition of water
  6. extractionthe reaction mixture was extracted with EtOAc (3×25 ml)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-967390107d4b4f5196ca69d12e7ed8e2
Source dataset
uspto-grants-2013_07
Patent number
US08492549B2

Reaction notes

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