Hydrogen Bromide → 3-{4-[(Dimethylamino)methyl]tetrahydro-pyran-4-yl}phenol

HRID 272810Notes

Reaction equation

HRID 272810 reaction equation
C[S-].[Na+].C[O:5][C:6]1[CH:7]=[C:8]([C:12]2([CH2:18][N:19]([CH3:21])[CH3:20])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[CH:9]=[CH:10][CH:11]=1.Br.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[CH3:21][N:19]([CH2:18][C:12]1([C:8]2[CH:7]=[C:6]([OH:5])[CH:11]=[CH:10][CH:9]=2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[CH3:20]

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 516892Sodium BicarbonateHCID 4378561Sodium methanethiolateHCID 68576409HCID 68576409, compound

Product 1

HCID 685763243-{4-[(Dimethylamino)methyl]tetrahydro-pyran-4-yl}phenolYield 35.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

To a suspension of Sodium thiomethoxide (0.42 g, 6 mmol) in DMF (1.2 mL) was added N-{[4-(3-methoxyphenyl)tetrahydro-pyran-4-yl]methyl}-N,N-dimethylamine (0.3 g, 1.2 mmol) and the resulting mixture was heated to 65° C. for 7 h, allowed to cool to ambient temperature and quenched with saturated aqueous NH4Cl (6 mL). The mixture was extracted with DCM, dried over Na2SO4, filtered and concentrated in vacuo to provide 0.25 g of crude product. A mixture of the crude and HBr (3 mL) was heated to reflux for 1 h. After cooling, water was added to quench the reaction and the mixture was basified with NaHCO3 and extracted with DCM. The organic extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (DCM/MeOH (10% NH3)) to provide 3-{4-[(dimethylamino)methyl]tetrahydro-pyran-4-yl}phenol (0.100 g, 35.5%).

Workup

  1. temperatureto cool to ambient temperature
  2. customquenched with saturated aqueous NH4Cl (6 mL)
  3. extractionThe mixture was extracted with DCM
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide 0.25 g of crude product
  8. temperaturewas heated
  9. temperatureto reflux for 1 h
  10. temperatureAfter cooling
  11. customto quench
  12. customthe reaction
  13. extractionextracted with DCM
  14. dry with materialThe organic extracts were dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe residue was purified by flash chromatography (DCM/MeOH (10% NH3))

Sources & evidence

ORD record
ord-2e1a3830db5d4b0fbb32eb3fc5c1ab90
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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