2-Methyl-5-hydroxypyridine → 2-Methyl-5-(1-(phenylthio)cyclopropoxy)pyridine

HRID 1038577Notes

Reaction equation

HRID 1038577 reaction equation
[CH:1]1([S:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:3][CH2:2]1.C([Li])CCC.IN1C(=O)CCC1=O.C(=O)([O-])O.[Na+].[OH:29][C:30]1[CH:31]=[CH:32][C:33]([CH3:36])=[N:34][CH:35]=1.IC1(SC2C=CC=CC=2)CC1>O1CCCC1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2].C(O)(=O)C>[CH3:36][C:33]1[CH:32]=[CH:31][C:30]([O:29][C:1]2([S:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:3][CH2:2]2)=[CH:35][N:34]=1

Participants

11

Reactant 6

HCID 142752-Methyl-5-hydroxypyridineHCID 120273N-IodosuccinimideHCID 123348Benzene, (cyclopropylthio)-2×HCID 516892Sodium BicarbonateHCID 11000298(1-Iodocyclopropyl)(phenyl)sulfane2×HCID 178418339Butyllithium

Product 1

HCID 665988332-Methyl-5-(1-(phenylthio)cyclopropoxy)pyridineYield 44%

Reagents, catalysts & solvents 4

HCID 178418647HCID 178418647, compoundCatalystHCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Cyclopropylphenylthioether (5.0 g, 33.3 mmol) was dissolved in tetrahydrofuran (50 mL), and n-butyllithium (25.1 mL, 39.9 mmol) was dropped for 5 minutes under an argon atmosphere at 0° C. Then, at −78° C., a solution of N-iodosuccinimide (8.99 g, 39.9 mmol) in tetrahydrofuran (100 mL) was dropped. The mixture was stirred overnight and allowed to warm gradually to room temperature. The reaction solution was added a saturated aqueous solution of sodium hydrogen carbonate, and extracted with hexane. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by silica-gel column chromatography (hexane). A crude product (5.64 g) ((1-iodocyclopropyl)(phenyl)sulfane:cyclopropylphenylthioether=2.4:1) was obtained. Then, 5-hydroxy-2-methylpyridine (1.82 g, 16.7 mmol) was dissolved in toluene (150 mL), added silver carbonate (9.19 g, 33.3 mmol), and a mixture of (1-iodocyclopropyl)(phenyl)sulfane:cyclopropylphenylthioether (=2.4:1) (5.64 g, 16.7 mmol (*converted in terms of the amount of (1-iodocyclopropyl)(phenyl) sulfane), and the mixture was stirred at room temperature overnight. Then, acetic acid (200 mL) was added and stirred for 10 minutes. The reaction solution was filtered through a pad of celite, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate), and the title compound (1.88 g (yield 44%)) was obtained as a yellow oil.

Workup

  1. extractionextracted with hexane
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. custompurified by silica-gel column chromatography (hexane)
  6. customA crude product (5.64 g) ((1-iodocyclopropyl)(phenyl)sulfane:cyclopropylphenylthioether=2.4:1) was obtained
  7. stirringwas stirred at room temperature overnight
  8. stirringstirred for 10 minutes
  9. filtrationThe reaction solution was filtered through a pad of celite
  10. concentrationconcentrated in vacuo
  11. customThe obtained residue was purified by silica-gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-457cd40189424cddb1ebbe872e3da550
Source dataset
uspto-grants-2013_10
Patent number
US08551985B2

Reaction notes

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