3-Hydroxypyridine → 3-(Oxiran-2-ylmethoxy)pyridine

HRID 1794778Notes

Reaction equation

HRID 1794778 reaction equation
[H-].[Na+].[N:3]1[CH:8]=[CH:7][CH:6]=[C:5]([OH:9])[CH:4]=1.[N+](C1C=C(S(O[CH2:23][C@@H:24]2[CH2:26][O:25]2)(=O)=O)C=CC=1)([O-])=O>CN(C)C=O>[O:25]1[CH2:26][CH:24]1[CH2:23][O:9][C:5]1[CH:4]=[N:3][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 79713-HydroxypyridineHCID 24758Sodium hydrideHCID 146490Benzenesulfonic acid, 3-nitro-, (2S)-2-oxiranylmethyl ester

Product 1

HCID 98774203-(Oxiran-2-ylmethoxy)pyridineYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (60%, 2.16 g, 54.0 mmol) was added portionwise into N,N-dimethylformamide (50 mL) with stirring at room temperature under a nitrogen atmosphere. A solution of 3-pyridinol (4.5 g, 46.28 mmol) in N,N-dimethylformamide (50 mL) was then added dropwise to this suspension over a period of 0.5 hour. After stirring for 1 hour a solution of (2S)-oxiranylmethyl 3-nitrobenzenesulfonate (10 g, 38.57 mmol) in N,N-dimethylformamide (50 mL) was added dropwise into this mixture over a period of 15 minutes. The mixture was then stirred at room temperature overnight. The reaction was quenched with aqueous ammonium chloride to pH 5 and extracted with ethyl acetate. The extracts were washed with water and dried with brine. Evaporation and purification by flash column chromatography (dichloromethane/methyl alcohol 95/5) gave a brown oil (1.44 g, 25% yield); 1H NMR (400 MHz, DMSO-d6) δ 2.71–2.73 (m, 1 H), 2.81–2.84 (m, 1 H), 3.34–3.38 (m, 1 H), 3.87–3.92 (m, 1 H), 4.40–4.43 (m, 1 H), 7.30–7.33 (m, 1 H), 7.39–7.41 (m, 1 H), 8.71–8.19 (m, 1 H), 8.31 (s, 1 H); MS (ES) m/z: 152 (MH+).

Workup

  1. additionwas added dropwise into this mixture over a period of 15 minutes
  2. stirringThe mixture was then stirred at room temperature overnight
  3. customThe reaction was quenched with aqueous ammonium chloride to pH 5
  4. extractionextracted with ethyl acetate
  5. washThe extracts were washed with water
  6. dry with materialdried with brine
  7. customEvaporation and purification by flash column chromatography (dichloromethane/methyl alcohol 95/5)

Sources & evidence

ORD record
ord-941937ac0e8649e5bf80b439854ba507
Source dataset
uspto-grants-2006_04
Patent number
US07022716B2

Reaction notes

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