Triethylamine → (2-Methoxy-6-methylbenzyl)phthalimide

HRID 8904

Reaction equation

HRID 8904 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:4]=1[CH2:5]O.C(N(CC)CC)C.CS(Cl)(=O)=O.[C:24]1(=[O:34])[NH:28][C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12.[K]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O.[Cl-].[Na+].O.O>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:7]([CH3:11])[C:4]=1[CH2:5][C:33]1[CH:32]=[CH:31][CH:30]=[C:26]2[C:27]([NH:28][C:24](=[O:34])[C:25]=12)=[O:29]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 13208697(2-Methoxy-6-methylphenyl)methanolHCID 24194345Phthalimide potassium salt

Product 1

HCID 21985073(2-Methoxy-6-methylbenzyl)phthalimideYield 66.4%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 2-methoxy-6-methylbenzyl alcohol (0.96 g, 6.32 mmol) in CH2Cl2 (35 mL) was added triethylamine (2.00 mL, 14.35 mmol) followed by methanesulfonyl chloride (0.90 mL, 11.63 mmol) and the resultant solution was heated at 40° C. for 45 minutes then cooled to room temperature. The mixture was diluted with CH2Cl2 (35 mL), washed with brine (3×15 mL), dried (Na2SO4), and concentrated to provide a pale yellow solid. The solid (1.12 g) was dissolved in DMF (35 mL), treated with potassium phthalimide (2.62 g, 14.15 mmol), and heated at 80° C. overnight. The mixture was cooled to room temperature and diluted with EtOAc (70 mL), brine (35 mL), and water (20 mL). The phases were separated and the organic phase was washed with 1.0 N NaOH (6×10 mL) and brine (2×20 mL). The organic phase was dried (MgSO4) and concentrated to provide an pale yellow solid. The solid was rinsed with hexanes (3×10 mL) and provided 1.18 g (66%) of (2-methoxy-6-methylbenzyl)phthalimide as a white solid. 1H NMR (CDCl3) δ 2.53 (s, 3H), 3.75 (s, 3H), 4.89 (s, 2H), 6.70 (d, 1H, J=8.4 Hz), 6.80 (d, 1H, J=7.5 Hz), 7.15 (dd, 1H, J=7.5, 8.4 Hz), 7.66–7.68 (m, 2H), 7.76–7.80 (m, 2H); 13C NMR (CDCl3) δ 20.27, 34.95, 55.90, 108.61, 122.38, 123.17, 123.41, 128.97, 132.60, 134.07, 139.55, 158.70, 168.36.

Workup

  1. washwashed with brine (3×15 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customto provide a pale yellow solid
  5. temperatureheated at 80° C. overnight
  6. temperatureThe mixture was cooled to room temperature
  7. customThe phases were separated
  8. washthe organic phase was washed with 1.0 N NaOH (6×10 mL) and brine (2×20 mL)
  9. dry with materialThe organic phase was dried (MgSO4)
  10. concentrationconcentrated
  11. customto provide an pale yellow solid
  12. washThe solid was rinsed with hexanes (3×10 mL)

Sources & evidence

ORD record
ord-7ef5756414e1483ebd37c8a4117aa494
Source dataset
uspto-grants-2006_08
Patent number
US07091217B2

Linked notes

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