Methyl iodide → HCID 18332474, compound

HRID 369121Notes

Reaction equation

HRID 369121 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:15][O:16][CH:17]([O:19][CH2:20][CH3:21])[CH3:18])=[O:8])[O:4][N:3]=1.[BH4-].[Na+].[CH3:24]I.[H-].[Na+]>[Cl-].[Na+].O.CCOCC.CN(C)C=O.CO.O1CCCC1>[CH2:20]([O:19][CH:17]([O:16][CH2:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[CH:7]([C:5]1[O:4][N:3]=[C:2]([CH3:1])[CH:6]=1)[O:8][CH3:24])[CH3:18])[CH3:21]

Participants

10

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 4311764Sodium borohydrideHCID 18332480HCID 18332480, compound

Product 1

HCID 18332474HCID 18332474, compoundYield 94.7%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a mixture of 3.18 g (11 mmol) of 2-(1-ethoxyethyl)oxymethylphenyl 3-methylisoxazol-5-yl ketone, 11 ml of tetrahydrofuran and 11 ml of methanol was added 0.42 g (11 mmol) of sodium borohydride under ice-cooling and stirred at room temperature for an hour. After completion of the reaction, 300 ml of brine was added and extracted twice with 100 ml of dichloromethane. The extract was dried over anhydrous magnesium and concentrated under reduced pressure to give 3.30 g of a crude product of 5-[2-(1-ethoxyethyl)oxymethyl-α-hydroxybenzyl]-3-methylisoxazole. To the crude product, 22 ml of N,N-dimethylformamide and 1.03 ml (16.5 mmol) of methyl iodide was added and then 0.57 g (14.3 mmol) of 60% sodium hydride was added under ice-cooling and stirred at the same temperature for an hour. After completion of the reaction, 200 ml of ether was added and washed twice with 200 ml of brine. The ether layer was dried over anhydrous magnesium and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 5-[2-(1-ethoxyethyl)oxymethyl-α-methoxybenzyl]-3-methylisoxazole (3.18 g, 94.7%) as colorless oil.

Workup

  1. temperaturecooling
  2. additionwas added
  3. extractionextracted twice with 100 ml of dichloromethane
  4. dry with materialThe extract was dried over anhydrous magnesium
  5. concentrationconcentrated under reduced pressure
  6. customto give 3.30 g of a crude product of 5-[2-(1-ethoxyethyl)oxymethyl-α-hydroxybenzyl]-3-methylisoxazole
  7. temperaturecooling
  8. stirringstirred at the same temperature for an hour
  9. additionwas added
  10. washwashed twice with 200 ml of brine
  11. dry with materialThe ether layer was dried over anhydrous magnesium
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-7c2b8cc6bc3744cdbcb232b2adc453b8
Source dataset
uspto-grants-2000_10
Patent number
US06136837

Reaction notes

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