Triphenylphosphine → N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-4-[(4-fluorophenyl)ethynyl]benzamide

HRID 551939Notes

Reaction equation

HRID 551939 reaction equation
Br[C:2]1[CH:31]=[CH:30][C:5]([C:6]([N:8]([CH2:22][CH2:23][CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[C:9]2[CH:10]=[CH:11][C:12]3[C:17](=[O:18])[O:16][C:15]([CH3:20])([CH3:19])[O:14][C:13]=3[CH:21]=2)=[O:7])=[CH:4][CH:3]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]#[CH:40])=[CH:35][CH:34]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.CCOCC>[CH:25]1([CH2:24][CH2:23][CH2:22][N:8]([C:9]2[CH:10]=[CH:11][C:12]3[C:17](=[O:18])[O:16][C:15]([CH3:20])([CH3:19])[O:14][C:13]=3[CH:21]=2)[C:6](=[O:7])[C:5]2[CH:4]=[CH:3][C:2]([C:40]#[C:39][C:36]3[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=3)=[CH:31][CH:30]=2)[CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 5226271-Ethynyl-4-fluorobenzeneHCID 575545704-bromo-N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)benzamide

Product 1

HCID 11562730N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-4-[(4-fluorophenyl)ethynyl]benzamideYield 84%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-bromo-N-(3-cyclopentylpropyl)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)benzamide (355 mg, 0.73 mmol), 4-fluorophenylacetylene (Apollo, 96 mg, 0.80 mmol), bis(triphenylphosphine)palladium(I) chloride (26 mg, 0.04 mmol), triphenylphosphine (38 mg, 0.15 mmol) and cuprous(I) iodide (7 mg, 0.04 mmol) in DMF (3 mL) and TEA (1 mL) was heated under microwave conditions at 120° C. for 25 min. The reaction mixture was then diluted with Et2O and the precipitate obtained was filtered off. Filtrate was then washed with an aqueous solution of HCl (1N) and brine. The organic layer was dried over MgSO4 and the solvents were removed under reduced pressure. Purification by flash chromatography on silicagel (EtOAc/c-Hex (10/90 to 20/80)) gave 321 mg (84%) of the title compound. HPLC, Rt: 5.67 min (purity: 97.9%). 1H NMR (CDCl3) δ: 7.78 (d, J=8.3 Hz, 1H), 7.44 (m, 2H), 7.31 (AB, J=8.4, Δ=12 Hz, 4H), 7.01 (t, J=8.5 Hz, 2H), 6.75 (dd, J=8.3, 2.1 Hz, 1H), 6.58 (d, J=2.1 Hz, 1H), 3.91 (t, J=7.7 Hz, 2H), 1.40-1.71 (m, 15H), 1.34 (m, 2H), 1.03 (m, 2H).

Workup

  1. customthe precipitate obtained
  2. filtrationwas filtered off
  3. washFiltrate was then washed with an aqueous solution of HCl (1N) and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvents were removed under reduced pressure
  6. customPurification by flash chromatography on silicagel (EtOAc/c-Hex (10/90 to 20/80))

Sources & evidence

ORD record
ord-200d4acae0f94953832a7fa375c8876d
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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