p-Toluenesulfonic acid monohydrate → HCID 67099918, compound

HRID 1868948Notes

Reaction equation

HRID 1868948 reaction equation
[Cl:1][C:2]1[C:3](I)=[C:4]([C:8]2([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[CH2:20]([O:22][C:23](OCC)([O:26]CC)[C:24]#[CH:25])[CH3:21].O.CC1C=CC(S(O)(=O)=O)=CC=1>C(#N)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[C:3]([C:25]#[C:24][C:23]([O:22][CH2:20][CH3:21])=[O:26])=[C:4]([C:8]2([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 109209723,3,3-Triethoxyprop-1-yneHCID 67099953HCID 67099953, compound

Product 1

HCID 67099918HCID 67099918, compoundYield 97.9%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of ethyl 4-(3-chloro-2-iodophenyl)-tetrahydro-2H-pyran-4-carboxylate (0.57 g, 1.4 mmol) and TEA (1.8 mL, 13 mmol) in 10 mL ACN was degassed by vacuum and back filled with nitrogen 3 times. The mixture was treated with 3,3,3-triethoxyprop-1-yne (0.37 g, 2.2 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.051 g, 0.072 mmol) and copper(I) iodide (0.028 g, 0.14 mmol) and stirred at 55° C. for 2 hours. The mixture was cooled to room temperature and concentrated. The residue was diluted with 50 mL EtOH and 10 mL water. The mixture was treated with 4-methylbenzenesulfonic acid hydrate (0.105 g, 0.551 mmol) and stirred at room temperature for 2 hours. The mixture was diluted with 100 mL EtOAc, washed with 20 mL saturated NaHCO3, dried over anhydrous Na2SO4 and concentrated. The crude product was purified by column chromatography (10-25% EtOAc/hexane) to give 0.5 g yellow oil. MS m/e: (M+H)+ 365.

Workup

  1. customwas degassed by vacuum
  2. additionback filled with nitrogen 3 times
  3. temperatureThe mixture was cooled to room temperature
  4. concentrationconcentrated
  5. additionThe residue was diluted with 50 mL EtOH and 10 mL water
  6. stirringstirred at room temperature for 2 hours
  7. washwashed with 20 mL saturated NaHCO3
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (10-25% EtOAc/hexane)

Sources & evidence

ORD record
ord-c82c2269072042d1ad12dcb6daa6c422
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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