Triphenylphosphine → Methyl 5-[({4-[(4-butylphenyl)ethynyl]phenyl}sulfonyl)(hexyl)amino]-2-fluorobenzoate

HRID 551986Notes

Reaction equation

HRID 551986 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:12]2[CH:13]=[CH:14][C:15]([F:21])=[C:16]([CH:20]=2)[C:17]([O-:19])=[O:18])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:28]([C:32]1[CH:37]=[CH:36][C:35]([C:38]#[CH:39])=[CH:34][CH:33]=1)[CH2:29][CH2:30][CH3:31].[C:40]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.CCOCC.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.[I].[Cu]>[CH2:28]([C:32]1[CH:33]=[CH:34][C:35]([C:38]#[C:39][C:2]2[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[C:12]3[CH:13]=[CH:14][C:15]([F:21])=[C:16]([CH:20]=3)[C:17]([O:19][CH3:40])=[O:18])(=[O:10])=[O:9])=[CH:4][CH:3]=2)=[CH:36][CH:37]=1)[CH2:29][CH2:30][CH3:31]

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 27751321-Butyl-4-ethynylbenzeneHCID 866265855-[({4-Bromophenyl)sulfonyl](hexyl)amino]-2-fluorobenzoate

Product 1

HCID 57554500Methyl 5-[({4-[(4-butylphenyl)ethynyl]phenyl}sulfonyl)(hexyl)amino]-2-fluorobenzoateYield 221.5%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 178505378HCID 178505378, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-[({4-bromophenyl)sulfonyl](hexyl)amino]-2-fluorobenzoate (400 mg; 0.85 mmol) in DMF (15 mL) under nitrogen were added (p-butylphenyl)acetylene (0.16 mL; 0.93 mmol), bis(triphenylphosphine)palladium chloride (29.7 mg; 0.04 mmol), triphenylphosphine (44.4 mg; 0.17 mmol), copper iodine (8.1 mg; 0.04 mmol) and TEA (0.35 mL; 2.54 mmol). The reaction mixture was stirred under MW at 120° C. for 1500 s. The mixture was diluted with Et2O (75 mL) and the precipitate obtained filtrated off. Filtrate was washed with HCl 1N and with brine. The organic layer was dried over magnesium sulfate and the solvent was removed under reduced pressure. Purification by flash chromatography on silicagel (c-Hex/EtOAc, 95:5 then 90:10) gave 207 mg (44.5%) of the title compound as a yellow cream. HPLC, Rt: 6.17 min (purity=98.5%). LC/MS: M+(ESI): 500.3, 1H NMR (CDCl3) δ: 7.55 (m, 6H), 7.32 (m, 1H), 7.10 (m, 4H), 3.91 (s, 3H), 3.52 (t, J=6.9 Hz, 2H), 2.63 (t, J=7.9 Hz, 2H), 1.30 (m, 12H), 0.95 (m, 3H), 0.85 (t, 3H.

Workup

  1. customthe precipitate obtained
  2. filtrationfiltrated off
  3. washFiltrate was washed with HCl 1N and with brine
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customPurification by flash chromatography on silicagel (c-Hex/EtOAc, 95:5

Sources & evidence

ORD record
ord-1c7390b978cf47a4b64fed4d53339403
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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