o-Fluorostyrene → 3-fluoro-1-[2-({4-[(E)-2-(2-fluorophenyl)vinyl]phenyl}sulfonyl)benzyl]piperidine

HRID 2376974

Reaktionsgleichung

Reaktionsgleichung von HRID 2376974
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:24]=[CH:23][CH:22]=[CH:21][C:12]=2[CH2:13][N:14]2[CH2:19][CH2:18][CH2:17][CH:16]([F:20])[CH2:15]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.FC1CCCNC1.[F:32][C:33]1[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=1[CH:35]=[CH2:36].C([O-])(=O)C.[Na+]>CN1CCCC1=O.[Pd]Cl>[F:20][CH:16]1[CH2:17][CH2:18][CH2:19][N:14]([CH2:13][C:12]2[CH:21]=[CH:22][CH:23]=[CH:24][C:11]=2[S:8]([C:5]2[CH:6]=[CH:7][C:2](/[CH:36]=[CH:35]/[C:34]3[CH:37]=[CH:38][CH:39]=[CH:40][C:33]=3[F:32])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:15]1

Komponenten

7

Edukt 4

HCID 123056o-FluorostyreneHCID 517045Sodium AcetateHCID 27591573-FluoropiperidineHCID 210993831-{2-[(4-Bromophenyl)sulfonyl]benzyl}-3-fluoropiperidine

Produkt 1

HCID 210994933-fluoro-1-[2-({4-[(E)-2-(2-fluorophenyl)vinyl]phenyl}sulfonyl)benzyl]piperidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178479784chloropalladiumKatalysatorHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

1-{2-[(4-Bromophenyl)sulfonyl]benzyl}-3-fluoropiperidine (prepared according to the methods of Example 75 Step 1 followed by Example 74 using 3-fluoropiperidine; 63 mg, 0.152 mmol), 2-fluorostyrene (36 μL, 0.3 mmol), sodium acetate (25 mg, 0.3 mmol) and palladium(I) chloride (1 mg) were combined in 1-methyl-2-pyrrolidinone (0.5 mL) and heated for 2 hours at 130° C. The cooled reaction mixture was partitioned between ethyl acetate and brine. The organic layer was washed further with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica, eluting with 30% ethyl acetate/isohexane, to give the title compound. δH (400 MHz, d6 DMSO): 8.19 (1H, d, J=6.3 Hz), 8.00-7.97 (2H, m), 7.86-7.82 (2H, m), 7.77 (4H, s), 7.48-7.34 (3H, m), 7.23-7.19 (2H, m), 5.15 (1H, d, J=49 Hz), 4.72 (1H, d, J=13.4 Hz), 4.45-4.40 (1H, m), 3.79-3.73 (1H, m), 3.55-3.51 (1H, m), 3.45-3.32 (2H, m), 3.20-3.14 (1H, m), 1.99-1.93 (2H, m), 1.73 (1H, d, J=12.1 Hz). m/z (ES+) 454 [MH+].

Aufarbeitung

  1. customThe cooled reaction mixture
  2. customwas partitioned between ethyl acetate and brine
  3. washThe organic layer was washed further with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica
  7. washeluting with 30% ethyl acetate/isohexane

Quellen und Nachweise

ORD-Eintrag
ord-2dc35e0bab564d018ecf2a3692461772
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07468393B2

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