Sodium Chloride → (S)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]-dioxin-2-yl)methyl]-3-methoxymethyl-3-methyl-piperidine

HRID 453828Notes

Reaction equation

HRID 453828 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@@:14]([CH2:19][OH:20])([CH3:18])[CH2:13]1.[OH-].[Na+].[CH3:23]I.[Na+].[Cl-]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.CCOC(C)=O.O>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@@:14]([CH2:19][O:20][CH3:23])([CH3:18])[CH2:13]1

Participants

9

Reactant 4

HCID 5234Sodium ChlorideHCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 25176123{(S)-1-[(S)-1-(2,3-Dihydrobenzo[1,4]dioxin-2-yl)methyl]-3-methylpiperidin-3-yl}methanol

Product 1

HCID 25176449(S)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]-dioxin-2-yl)methyl]-3-methoxymethyl-3-methyl-piperidineYield 19.3%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of {(S)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)methyl]-3-methyl-piperidin-3-yl}methanol (134 mg, 0.48 mmol), tetrabutylammonium bromide (0.031 mg, 0.10 mmol) and 50% NaOH solution (2 ml) in toluene (2 ml) was stirred at room temperature for 15 min. Methyl iodide (0.24 ml, 3.86 mmol) was added drop wise and the mixture was stirred for 6 h 45 min. Saturated NaCl, water and EtOAc were added and the phases were separated. The aqueous phase was extracted twice with EtOAc and combined organic phases were washed with water and saturated NaCl. The organic phase was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified with flash chromatography using gradient of heptane and EtOAc as eluent to give 27 mg of the title compound.

Workup

  1. stirringthe mixture was stirred for 6 h 45 min
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted twice with EtOAc
  4. washwere washed with water and saturated NaCl
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude product was purified with flash chromatography

Sources & evidence

ORD record
ord-f727fc1ba23b49a7b7b1cab1b1833e5d
Source dataset
uspto-grants-2013_07
Patent number
US08492549B2

Reaction notes

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