Chloromethyl Methyl Ether → 2-(4-t-Butylphenyl)-3-methoxymethyloxy-4-ethoxycarbonylthiophene

HRID 2103796Notes

Reaction equation

HRID 2103796 reaction equation
[H-].[Na+].[C:3]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][CH:15]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:17]=2[OH:18])=[CH:9][CH:8]=1)([CH3:6])([CH3:5])[CH3:4].[CH3:24][O:25][CH2:26]Cl.[Cl-].[NH4+]>CN(C)C=O>[C:3]([C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:14][CH:15]=[C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:17]=2[O:18][CH2:24][O:25][CH3:26])=[CH:11][CH:12]=1)([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 670503332-(4-t-Butylphenyl)-3-hydroxy-4-ethoxycarbonylthiophene

Product 1

HCID 670503162-(4-t-Butylphenyl)-3-methoxymethyloxy-4-ethoxycarbonylthiopheneYield 92.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

60% Sodium hydride (28 mg, 0.69 mmol) was added to a solution of 2-(4-t-butylphenyl)-3-hydroxy-4-ethoxycarbonylthiophene (0.20 g, 0.66 mmol) obtained in accordance with JP-A-48-26755 in dimethylformamide (1.0 mL) at room temperature, and the reaction solution was stirred at 60° C. for 15 minutes. After the reaction solution was cooled to room temperature, chloromethyl methyl ether (0.055 mL, 0.73 mmol) was added dropwise, and the reaction solution was stirred at room temperature for another 5 hours. After addition of saturated aqueous ammonium chloride, the reaction solution was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate. The organic layer was concentrated and purified by silica gel column chromatography (chloroform) to give the desired product as a colorless oil (212 mg, yield 91%).

Workup

  1. temperatureAfter the reaction solution was cooled to room temperature
  2. stirringthe reaction solution was stirred at room temperature for another 5 hours
  3. extractionthe reaction solution was extracted with ethyl acetate
  4. washthe organic layer was washed with saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationThe organic layer was concentrated
  7. custompurified by silica gel column chromatography (chloroform)

Sources & evidence

ORD record
ord-221bbd2dd87b403786bed0ec80159d65
Source dataset
uspto-grants-2009_08
Patent number
US07576115B2

Reaction notes

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