Acetic Acid → HCID 22241510, compound

HRID 892216Notes

Reaction equation

HRID 892216 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[CH:9]=[C:10]([C:14]#[C:15][Si](C)(C)C)[CH:11]=[CH:12][CH:13]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=O)C>C1COCC1>[C:14]([C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([O:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:9]=1)#[CH:15]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium FluorideHCID 22241280HCID 22241280, compound

Product 1

HCID 22241510HCID 22241510, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

[3-(2-Methoxy-ethoxymethoxy)-phenylethynyl]-trimethyl silane (0.57 g, 2 mmol, example 97) and 1.0 M tetrabutylammonium fluoride (2.1 mL, 2 mmol) are added to THF (10 mL) and acetic acid (0.13 g, 2 mmol) is added and this mixture is stirred at 20° C., under nitrogen. After 15 minutes, the solvent is removed in vacuo and the residue is azeotroped with benzene and purified by flash chromatography (silica, 20% ethyl acetate, 30% dichloromethane in hexanes) to give 1-ethynyl-3-(2-methoxy-ethoxymethoxy)-benzene (0.28 g, 1.4 mmol) which is dissolved in THF (8 mL), cooled to −78° C., under nitrogen and to this solution is added 2.5M n-butyl lithium (0.56 mL, 1.4 mmol) dropwise over 30 seconds. After stirring for 15 minutes, 1.0M zinc chloride in ether (1.4 mL, 1.4 mmol) is added dropwise over 30 seconds and this mixture is stirred for 30 minutes. Bis-(dibenzylideneacetone) palladium (0.04 g, 0.07 mmol) and bis (diphenyl phosphino) ferrocene (0.04 g, 0.07 mmol) is added and to this mixture is added ethyl-2-methyl-6-trifluoromethanesulfonyloxy benzoate (0.44 g, 1.4 mmol, 95) in THF (2 mL). The cooling bath is removed and the reaction allowed to warm to room temperature. Then the reaction mixture is heated in an oil bath at 65° C. overnight. The reaction is then diluted with ethyl acetate (50 mL), washed with saturated ammonium chloride and brine and then dried over magnesium sulfate. The solvent is removed in vacuo and the residue purified by flash chromatography (silica, 10% ethyl acetate, 25% dichloromethane in hexanes) to give the title compound. MS (ESI) 369 (M+H)+.

Workup

  1. additionis added
  2. customthe solvent is removed in vacuo
  3. customthe residue is azeotroped with benzene
  4. custompurified by flash chromatography (silica, 20% ethyl acetate, 30% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-4abc665bd6404d3e978c12d46a278832
Source dataset
uspto-grants-2006_02
Patent number
US07005440B1

Reaction notes

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