4-(2-Propyn-1-yl)morpholine → methyl (E)-[2-methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyl-oxy]phenoxy]acetate

HRID 1039485Notes

Reaction equation

HRID 1039485 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1)[C:2]#[CH:3].I[C:11]1[CH:16]=[CH:15][C:14](/[C:17](/[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)=[CH:18]\[CH2:19][O:20][C:21]2[CH:32]=[CH:31][C:24]([O:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])=[C:23]([CH3:33])[CH:22]=2)=[CH:13][CH:12]=1>O1CCCC1.C(N(CC)CC)C.[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:33][C:23]1[CH:22]=[C:21]([O:20][CH2:19]/[CH:18]=[C:17](\[C:14]2[CH:15]=[CH:16][C:11]([C:3]#[C:2][CH2:1][N:4]3[CH2:9][CH2:8][O:7][CH2:6][CH2:5]3)=[CH:12][CH:13]=2)/[C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)[CH:32]=[CH:31][C:24]=1[O:25][CH2:26][C:27]([O:29][CH3:30])=[O:28]

Participants

7

Reactant 2

HCID 4129414-(2-Propyn-1-yl)morpholineHCID 86629302methyl (E)-[4-[3-(4-iodophenyl)-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate

Product 1

HCID 86629301methyl (E)-[2-methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyl-oxy]phenoxy]acetate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

N-Propargylmorpholine (171 mg, 1.37 mmol) was added to a solution of methyl (E)-[4-[3-(4-iodophenyl)-3-(3-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate (400 mg, 0.68 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, 0.108 mmol) and tetrakis(triphenylphosphine)-palladium (62 mg, 0.054 mmol) were added. The reaction mixture was degassed once more and then stirred at ambient temperature for 2 days under argon. The mixture was evaporated in vacuo; the residue was dissolved in ethyl acetate (50 mL) and the solution was washed with water (2×15 mL) and brine (10 mL). The organic solution was dried with anhydrous magnesium sulfate and its evaporation gave oil that was purified by flash column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 1:1) yielding methyl (E)-[2-methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(3-trifluoromethylphenyl)allyl-oxy]phenoxy]acetate as oil.

Workup

  1. customThe mixture was degassed
  2. customThe reaction mixture was degassed once more
  3. customThe mixture was evaporated in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  5. washthe solution was washed with water (2×15 mL) and brine (10 mL)
  6. dry with materialThe organic solution was dried with anhydrous magnesium sulfate and its evaporation
  7. customgave oil that
  8. customwas purified by flash column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-df619d9c94b541fca5097de22ccf5e45
Source dataset
uspto-grants-2013_10
Patent number
US08551993B2

Reaction notes

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