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

HRID 2376974Notes

Reaction equation

HRID 2376974 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178479784chloropalladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

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+].

Workup

  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

Sources & evidence

ORD record
ord-2dc35e0bab564d018ecf2a3692461772
Source dataset
uspto-grants-2008_12
Patent number
US07468393B2

Reaction notes

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