Methyl iodide → HCID 18994276, compound

HRID 1647508Notes

Reaction equation

HRID 1647508 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2([OH:14])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH3:17]I>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2([O:14][CH3:17])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 19925593HCID 19925593, compound

Product 1

HCID 18994276HCID 18994276, compoundYield 77.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(3-aminophenyl)-4-hydroxytetrahydropyran (630 mg, 3.26 mmol), prepared as in step 3, in dry DMF (13 mL) was added sodium hydride (326 mg of a 60% oil dispersion). The reaction was stirred at ambient temperature for 1 hour and then methyl iodide (0.24 mL, 3.19 mmol) was added neat. The resulting solution was stirred at ambient temperature for 0.5 hour and quenched with saturated aqueous ammonium chloride. The biphasic solution was extracted with ethyl acetate. The organic layer was washed (1×, saturated aqueous ammonium chloride; 2×, brine), dried (MgSO4), and concentrated in vacuo to provide an oil. Chromatography on silica gel with 20% ethyl acetate/hexanes as the eluant provided 4-(3-aminophenyl)-4-methoxytetrahydropyran as a beige solid (510 mg, 76%). mp 99.0°-100.5° C. 1H NMR (300 MHz, CDCl3) δ7.17 (1H, t, J=9 Hz), 6.73- 6.82 (2H, m), 6.62 (1H, ddd, J=9, 2, 1 Hz), 3.85 (2H, td, J=10.5, 10.5, 2.5 Hz), 3.81 (2H, ddd, J=10.5, 9, 3 Hz), 2.99 (3H, s), 1.87-2.07 (4H, m). MS m/e 207 (M)+, 225 (M+NH4)+.

Workup

  1. stirringThe resulting solution was stirred at ambient temperature for 0.5 hour
  2. customquenched with saturated aqueous ammonium chloride
  3. extractionThe biphasic solution was extracted with ethyl acetate
  4. washThe organic layer was washed (1×, saturated aqueous ammonium chloride; 2×, brine)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto provide an oil

Sources & evidence

ORD record
ord-d0fd7b8f09b14c5eb7839c6800ddba37
Source dataset
uspto-grants-1995_07
Patent number
US05432194

Reaction notes

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