Sodium Iodide → 3-ethyl-6-methyl-5-(pyrrol-1-yl)-1H-pyridin-2-one

HRID 1921346Notes

Reaction equation

HRID 1921346 reaction equation
[CH2:1]([C:3]1[C:4]([O:15]C)=[N:5][C:6]([CH3:14])=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[CH:10]2)[CH:8]=1)[CH3:2].[I-].[Na+].C(#N)C.Cl[Si](C)(C)C>O>[CH2:1]([C:3]1[C:4](=[O:15])[NH:5][C:6]([CH3:14])=[C:7]([N:9]2[CH:10]=[CH:11][CH:12]=[CH:13]2)[CH:8]=1)[CH3:2]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 6342AcetonitrileHCID 6397ChlorotrimethylsilaneHCID 674922843-Ethyl-2-methoxy-6-methyl-5-pyrrol-1-yl-pyridine

Product 1

HCID 115722533-ethyl-6-methyl-5-(pyrrol-1-yl)-1H-pyridin-2-oneYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
65 °C

Procedure

To a mixture of 3-ethyl-2-methoxy-6-methyl-5-pyrrol-1-yl-pyridine (68 mg, 0.315 mmol) and sodium iodide (141 mg, 0.94 mmol) under a N2 atmosphere is added anhydrous acetonitrile (4 mL) followed by dropwise addition of chlorotrimethylsilane (118 μL, 0.940 mmol). The reaction mixture is stirred at 65° C. under nitrogen for 17 hr. The reaction mixture is allowed to cool, diluted with water and extracted with three portions of dichloromethane. The combined extracts are dried over magnesium sulfate and evaporated to leave an orange residue. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1). Clean fractions containing the product are combined and evaporated to give 3-ethyl-6-methyl-5-(pyrrol-1-yl)-1H-pyridin-2-one (59 mg, 93% yield) as a white solid. This material (49 mg) is dissolved in dichloromethane (2 mL) and treated with ethereal hydrochloric acid (2.0M, 0.49 mL). The solution is stirred for 1.5 hr and then evaporated to give 3-ethyl-6-methyl-5-pyrrol-1-yl-1H-pyridin-2-one hydrochloride (54 mg) as an off-white solid. LC/MS: RT: 2.70 min, MS: m/e=203 (M+H); 1H NMR (δ ppm): 11.75 (1H, s), 7.16 (1H, s), 6.80 (2H, t), 6.16 (2H, t), 2.38 (2H, q), 1.97 (3H, s), 1.08 (3H, t).

Workup

  1. temperatureto cool
  2. extractionextracted with three portions of dichloromethane
  3. dry with materialThe combined extracts are dried over magnesium sulfate
  4. customevaporated
  5. customto leave an orange residue
  6. customThe crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1)
  7. additionClean fractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-35fb9563b58b42a58e43658414c867b8
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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