Methyl iodide → HCID 22721999, compound

HRID 1581512Notes

Reaction equation

HRID 1581512 reaction equation
[N:1]1[O:5][N:4]=[C:3]2[CH:6]=[C:7]([C:10]([N:12]3[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]3)=[O:11])[CH:8]=[CH:9][C:2]=12.[H-].[Na+].[CH3:21]I>CN(C)C=O.O>[N:1]1[O:5][N:4]=[C:3]2[CH:6]=[C:7]([C:10]([N:12]3[CH2:17][CH2:16][CH:15]([O:18][CH3:21])[CH2:14][CH2:13]3)=[O:11])[CH:8]=[CH:9][C:2]=12

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 9859709HCID 9859709, compound

Product 1

HCID 22721999HCID 22721999, compoundYield 30.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-(Benzofurazan-5-ylcarbonyl)-4-hydroxypiperidine (840 mg, 3.40 mmol) was dissolved in dimethylformamide (12 mL) and treated with 60% sodium hydride (150 mg, 3.75 mmol) for 30 minutes. Methyl iodide (650 mg, 4.54 mmol) was added, and, after 3 hours at room temperature, the reaction mixture was further treated with the same quantities of sodium hydride and methyl iodide as above and allowed to stand for 16 hr. The reaction solution was diluted with water and product was extracted into ethyl acetate. The organic solution was washed with water and saturated sodium chloride and dried over MgSO4. The crude product was purified by decolorization with charcoal in ethanol, twice chromatographed on silica gel by elution with hexane/ethyl acetate (2:1), and finally by kugelrohr distillation at 125-140° C. to yield 1-(benzofurazan-5-ylcarbonyl)-4-methoxypiperidine (269 mg, 30%) as a pale yellow oil. IR: 1639, 1440, 1274, 1101, and 1089 cm−1. 1H NMR (500 MHz): δ7.91 (1H, dm, J=9.2 Hz), 7.85 (1H, t, J=1.1 Hz), 7.43 (1H, dd, J=9.2 and 1.2 Hz), 3.90-4.05 (1H, m), 3.55-3.72 (2H, m), 3.53 (1H, sept, J=3.5 Hz), 3.38 (3H, s), 3.20-3.35 (1H, m), 1.90-2.02 (1H, m), 1.65-1.85 (2H, m), and −1.65 ppm (1H, m).

Workup

  1. waitto stand for 16 hr
  2. extractionwas extracted into ethyl acetate
  3. washThe organic solution was washed with water and saturated sodium chloride
  4. dry with materialdried over MgSO4
  5. customThe crude product was purified by decolorization with charcoal in ethanol
  6. customtwice chromatographed on silica gel by elution with hexane/ethyl acetate (2:1)
  7. distillationfinally by kugelrohr distillation at 125-140° C.

Sources & evidence

ORD record
ord-862c660134d248ac8174d0ebb0035f84
Source dataset
uspto-grants-2004_05
Patent number
US06730677B2

Reaction notes

Loading…