Methyl iodide → 4-(1-Methoxy-1-methyl-ethyl)-benzoic acid methyl ester

HRID 855297Notes

Reaction equation

HRID 855297 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([OH:15])([CH3:14])[CH3:13])=[CH:8][CH:7]=1.[CH3:17]I.[Cl-].[NH4+]>CN(C=O)C>[CH3:3][O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([O:15][CH3:17])([CH3:14])[CH3:13])=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 18174533Methyl 4-(2-hydroxypropan-2-yl)benzoate

Product 1

HCID 181744854-(1-Methoxy-1-methyl-ethyl)-benzoic acid methyl esterYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

439 mg of sodium hydride (60% in mineral oil) were suspended in 10 ml DMF and a solution of 1.64 g of 4-(1-hydroxy-1-methyl-ethyl)-benzoic acid methyl ester (8.4 mmol) in 10 ml DMF was added at 0° C. The mixture was allowed to warm to rt and was stirred for 1 h at this temperature before 0.79 ml of methyl iodide (12.7 mmol) were added. After 17 h additional 338 mg of sodium hydride (60% in mineral oil) and 0.53 ml methyl iodide (8.4 mmol) were added and stirring was continued for 20 h. Then saturated ammonium chloride solution was added and the mixture was extracted with EtOAc. The combined organic layers were washed with water and brine, dried with magnesium sulfate, filtered and the solvent was evaporated. Chromatographic purification (silica gel; c-hexane/EtOAc 9:1 to 4:1) of the remaining residue yielded 661 mg (38%) of 4-(1-methoxy-1-methyl-ethyl)-benzoic acid methyl ester as a colorless liquid. 1H NMR (CDCl3, 300 MHz): δ 1.54 (s, 6H), 3.09 (s, 3H), 3.92 (s, 3H), 7.48 (d, J=9 Hz, 1H), 8.02 (d, J=9 Hz, 1H).

Workup

  1. additionwere added
  2. extractionthe mixture was extracted with EtOAc
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customChromatographic purification (silica gel; c-hexane/EtOAc 9:1 to 4:1) of the remaining residue

Sources & evidence

ORD record
ord-e901a7077483444fb01cdac17508e0e4
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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