Acetic Acid → 2-Methyl-5-(1-(phenylthio)cyclopropoxy)pyridine

HRID 1690200Notes

Reaction equation

HRID 1690200 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.[OH:11][C:12]1[CH:13]=[CH:14][C:15]([CH3:18])=[N:16][CH:17]=1.C1(S)C=CC=CC=1.C(O)(=O)C>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH3:18][C:15]1[CH:14]=[CH:13][C:12]([O:11][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:17][N:16]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 7969ThiophenolHCID 142752-Methyl-5-hydroxypyridineHCID 123348Benzene, (cyclopropylthio)-2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 1140TolueneSolvent

Procedure

Cyclopropylphenyl thioether (5.0 g, 33.3 mmol) was dissolved in tetrahydrofuran (50 mL), and n-butyllithium (25.1 mL, 39.9 mmol) was dropwisely added at 0° C. for 5 minutes under an argon atmosphere. Then, a solution of N-iodosuccinimide (8.99 g, 39.9 mmol) in tetrahydrofuran (100 mL) was dropwisely added at −78° C. The resultant mixture was stirred overnight, and gradually warmed to room temperature. The reaction solution was added with 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 using silica-gel column chromatography (hexane), to obtain a crude product ((1-iodocyclopropyl)(phenyl)sulfane:cyclopropylphenylthioether (=2.4:1) (5.64 g). Next, 5-hydroxy-2-methylpyridine (1.82 g, 16.7 mmol) was dissolved in toluene (150 mL). The resultant mixture was added with silver carbonate (9.19 g, 33.3 mmol) and 1-iodocyclopropyl)(phenypsulfane:cyclopropylphenylthioether (=2.4:1) mixture (5.64 g, 16.7 mmol (*converted in terms of 1-iodocyclopropyl)(phenyl)sulfane), and stirred overnight at room temperature. Then, acetic acid (200 mL) was added thereto, and stirred for 10 minutes. The reaction solution was filtered using celite and concentrated in vacuo. The obtained residue was purified using silica-gel column chromatography (hexane/ethyl acetate), and 2-methyl-5-(1-(phenylthio)cyclopropoxy)pyridine (1.88 g, yield 44%) was obtained as a yellow oil.

Workup

  1. filtrationThe reaction solution was filtered
  2. concentrationconcentrated in vacuo
  3. customThe obtained residue was purified

Sources & evidence

ORD record
ord-bef17ab25f844f718923fb8a26d3c898
Source dataset
uspto-grants-2012_04
Patent number
US08153634B2

Reaction notes

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