3,4-dihydro-2H-pyran → 2-bromo-5-[2-methoxy-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyridine

HRID 1881897Notes

Reaction equation

HRID 1881897 reaction equation
[Br:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:12])[CH2:9][O:10][CH3:11])=[CH:4][CH:3]=1.[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])O.[Na+]>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([O:12][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][O:13]2)[CH2:9][O:10][CH3:11])=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 593315801-(6-Bromopyridin-3-yl)-2-methoxyethanol

Product 1

HCID 593313642-bromo-5-[2-methoxy-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyridineYield 94.6%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 1-(6-bromopyridin-3-yl)-2-methoxyethanol (15.26 g), p-toluenesulfonic acid monohydrate (0.63 g) and tetrahydrofuran (65 ml) was added 3,4-dihydro-2H-pyran (7.76 g) at room temperature over 30 min, and the mixture was stirred for 2 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography, and the title compound (19.66 g, yield 94%) was obtained as a colorless oil from a fraction eluted with ethyl acetate-hexane (2:3, volume ratio). MS: 318 (MH+).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-6201e15ca99544c1bd6d4c0da5b2b224
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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