N,N-Dimethylpropargylamine → methyl (E)-[4-[3-[4-[3-(N,N-dimethylamino)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

HRID 549871Notes

Reaction equation

HRID 549871 reaction equation
[CH3:1][N:2]([CH3:6])[CH2:3][C:4]#[CH:5].I[C:8]1[CH:13]=[CH:12][C:11](/[C:14](/[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=2)=[CH:15]\[CH2:16][O:17][C:18]2[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[C:20]([CH3:30])[CH:19]=2)=[CH:10][CH:9]=1>O1CCCC1.C(N(CC)CC)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][N:2]([CH2:3][C:4]#[C:5][C:8]1[CH:9]=[CH:10][C:11](/[C:14](/[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:39])[F:40])[CH:32]=2)=[CH:15]\[CH2:16][O:17][C:18]2[CH:29]=[CH:28][C:21]([O:22][CH2:23][C:24]([O:26][CH3:27])=[O:25])=[C:20]([CH3:30])[CH:19]=2)=[CH:12][CH:13]=1)[CH3:6]

Participants

7

Reactant 2

HCID 81643N,N-Dimethylpropargylamine2×HCID 86629302methyl (E)-[4-[3-(4-iodophenyl)-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

Product 1

HCID 86629304methyl (E)-[4-[3-[4-[3-(N,N-dimethylamino)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418397HCID 178418397, compoundCatalyst2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Dimethyl(prop-2-ynyl)amine (114 mg, 1.374 mmol) was added to a solution of methyl (E)-[4-[3-(4-iodophenyl)-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate (400 mg, 0.687 mmol; prepared as described in example 34) in a mixture of tetrahydrofuran (12 mL) and triethylamine (12 mL). The mixture was degassed and copper(I) iodide (20 mg, 0.109 mmol) and tetrakis(triphenylphosphine)palladium (63 mg, 0.054 mmol) were added. The reaction mixture was stirred at ambient temperature for 24 h. Further portions of dimethyl(prop-2-ynyl)amine (57 mg, 0.687 mmol), copper(I) iodide (10 mg, 0.0545 mmol) and tetrakis(triphenylphosphine)palladium (31.5 mg, 0.027 mmol) were added and the reaction mixture was stirred under argon for additional 20 h. The mixture was evaporated in vacuo; the residue was dissolved in ethyl acetate (30 mL) and was washed with water (2×15 mL) and brine (10 mL). The organic solution was dried with anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 3:5) yielding methyl (E)-[4-[3-[4-[3-(N,N-dimethylamino)propynyl]phenyl]-3-(3-trifluoromethyl phenyl)allyloxy]-2-methylphenoxy]acetate as oil.

Workup

  1. customThe mixture was degassed
  2. stirringthe reaction mixture was stirred under argon for additional 20 h
  3. customThe mixture was evaporated in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (30 mL)
  5. washwas washed with water (2×15 mL) and brine (10 mL)
  6. dry with materialThe organic solution was dried with anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 3:5)

Sources & evidence

ORD record
ord-bf01c6f6a1ad474bafacaed0e9bd6b52
Source dataset
uspto-grants-2011_05
Patent number
US07943613B2

Reaction notes

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