Methyl iodide → HCID 22905638, compound

HRID 1488460Notes

Reaction equation

HRID 1488460 reaction equation
[H-].[Na+].[C:3]([N:8]1[C:16]2[C:11](=[C:12]([CH3:19])[C:13]([OH:18])=[C:14]([CH3:17])[CH:15]=2)[CH:10]([CH3:20])[CH2:9]1)(=[O:7])[CH:4]([CH3:6])[CH3:5].[CH3:21]I>O1CCCC1>[C:3]([N:8]1[C:16]2[C:11](=[C:12]([CH3:19])[C:13]([O:18][CH3:21])=[C:14]([CH3:17])[CH:15]=2)[CH:10]([CH3:20])[CH2:9]1)(=[O:7])[CH:4]([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 22905634HCID 22905634, compound

Product 1

HCID 22905638HCID 22905638, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (7 mg, 0.18 mmol) contained in a round-bottom flask was washed using dry hexanes and tetrahydrofuran (2 mL) was added, and the suspension was stirred at 0° C. under nitrogen atmosphere. A solution of N-isobutyryl-5-hydroxy-3,4,6-trimethylindoline (11 b, 42 mg 0.17 mmol) dissolved in tetrahydrofuran (2 mL) was added dropwise using a syringe. Methyl iodide (0.2 mL) was added to the cold solution in one portion, and the mixture was heated under reflux for 17 h. The reaction mixture was cooled, quenched with saturated aq. ammonium chloride solution and extracted with ether. The combined extracts were washed with brine and dried (MgSO4). Removal of solvents gave a viscous liquid which was purified by flash column chromatography using 1:4 ethyl acetate:hexanes as eluent, to afford N-isobutyryl-5-methoxy-3,4,6-trimethylindoline (13, 40 mg, 90% yield) as a viscous liquid. Spectral data: 1H NMR: δ 1.20-1.35 (m, 9H), 2.22 (s, 3H), 2.27 (s, 3H), 2.74 (quintet, 1H, J=6.5 Hz), 3.30 (t, 1H, J=6.5 Hz), 3.65 (s, 3H), 3.76 (dd, 1H, J=10, 1 Hz), 4.15 (t, 1H, J=9 Hz), 8.0 (s, 1H).

Workup

  1. washwas washed
  2. additionwas added
  3. additionwas added dropwise
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for 17 h
  6. temperatureThe reaction mixture was cooled
  7. customquenched with saturated aq. ammonium chloride solution
  8. extractionextracted with ether
  9. washThe combined extracts were washed with brine
  10. dry with materialdried (MgSO4)
  11. customRemoval of solvents
  12. customgave a viscous liquid which
  13. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-37e90f46365841adacd6a3c5ec0e93dd
Source dataset
uspto-grants-1997_10
Patent number
US05674876

Reaction notes

Loading…