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

HRID 2376974

反応式

HRID 2376974 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178479784chloropalladium触媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
130 °C

実験手順

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+].

後処理

  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

出典と根拠

ORDレコード
ord-2dc35e0bab564d018ecf2a3692461772
出典データセット
uspto-grants-2008_12
特許番号
US07468393B2

関連ノート

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