5-Hexyn-1-ol → 2,2,2-trifluoro-N-(4-(6-hydroxyhex-1-yn-1-yl)phenyl)acetamide

HRID 1944870Notes

Reaction equation

HRID 1944870 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1)=[O:4].[CH2:15]([OH:21])[CH2:16][CH2:17][CH2:18][C:19]#[CH:20]>CN(C=O)C.C([O-])(=O)C.C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]([F:14])([F:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:20]#[C:19][CH2:18][CH2:17][CH2:16][CH2:15][OH:21])=[CH:8][CH:7]=1)=[O:4]

Participants

6

Reactant 2

HCID 702345-Hexyn-1-ol2×HCID 6869622,2,2-trifluoro-N-(4-iodophenyl)acetamide

Product 1

HCID 575169382,2,2-trifluoro-N-(4-(6-hydroxyhex-1-yn-1-yl)phenyl)acetamide

Reagents, catalysts & solvents 3

HCID 82707Tetrabutylammonium AcetateCatalyst2×HCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Procedure

A solution of Intermediate 32 (2.7 g, 8.5 mmol, prepared according to Melissaris, A. P. and Litt, M. H. J Org Chem 1994, 59, 5818-5821) in DMF (26 mL) was treated successively with tetra-n-butylammonium acetate (3.8 g, 13 mmol) and palladium (II) acetate (57 mg, 0.26 mmol). The mixture was degassed with nitrogen and then treated with 5-hexyn-1-ol (0.93 mL, 8.5 mmol). After four hours of stirring at room temperature, additional quantities of the following reagents were added: tetra-n-butylammonium acetate (1 g), palladium (II) acetate (57 mg), and 5-hexyn-1-ol (1 mL). After stirring overnight at room temperature, the mixture was partitioned between diethyl ether and water. The aqueous phase was extracted four times with diethyl ether. The combined organic extracts were washed twice with water and once with saturated aqueous sodium chloride solution before drying over anhydrous magnesium sulfate, filtration and concentration under reduced pressure to provide the title compound as brown syrup that partially solidified under vacuum. ES/MS calcd. for C14H15F3NO2+: 286.1. Found m/z=286.2 (M+H)+

Workup

  1. customThe mixture was degassed with nitrogen
  2. additionadditional quantities of the following reagents were added
  3. stirringAfter stirring overnight at room temperature
  4. customthe mixture was partitioned between diethyl ether and water
  5. extractionThe aqueous phase was extracted four times with diethyl ether
  6. washThe combined organic extracts were washed twice with water and once with saturated aqueous sodium chloride solution
  7. dry with materialbefore drying over anhydrous magnesium sulfate, filtration and concentration under reduced pressure

Sources & evidence

ORD record
ord-f8a2243a77554ac48b93ec1688c0d7f1
Source dataset
uspto-grants-2013_03
Patent number
US08394829B2

Reaction notes

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