4-Vinylpyridine → 5-(2-(4-Pyridinyl)vinyl)-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

HRID 365835ノート

反応式

HRID 365835 の反応式
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:13][CH2:12][N:11]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:5]=[N:6][CH:7]=1.[CH:21]([C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1)=[CH2:22].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:26]1[CH:27]=[CH:28][C:23]([CH:21]=[CH:22][C:2]2[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]3[CH2:13][CH2:12][N:11]3[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:5]=[N:6][CH:7]=2)=[CH:24][CH:25]=1

参加物

7

反応物 3

HCID 75024-VinylpyridineHCID 80271Tri-o-tolylphosphineHCID 10688713(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylate

生成物 1

HCID 538525935-(2-(4-Pyridinyl)vinyl)-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine収率 69%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6342Acetonitrile溶媒HCID 8471Triethylamine溶媒

実験手順

To a solution of 5-bromo-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 54b (1.03 g, 3.0 mmol) in acetonitrile (20 mL) and triethylamine (12.5 mL) was added 4-vinylpyridine (0.65 mL, 6 mmol), palladium acetate (125 mg, 0.56 mmol) and tri-o-tolylphosphine (625 mg). The mixture was heated at reflux for 16 hours. The solvent was removed, and the residue was washed with saturated sodium bicarbonate was added to free the amine, and the mixture was extracted with EtOAc, dried (MgSO4), and concentrated. The residue was chromatographed on a silica gel column, eluting with hexane:Et2O 1:2 to 0:1 to afford the title compound (760 mg, 69%). MS (CI/NH3) m/z 368 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.43 (s, 9H), 2.35 (m, 2H), 3.90 (m, 2H), 4.20 (m, 1H), 4.40 (m, 1H), 4.55 (m, 1H), 7.10 (m, 1H), 7.2 (m, 1H), 7.38 (m, 2H), 7.45 (br s, 1H), 8.29 (m, 1H), 8.37 (s, 1H), 8.61 (m, 2H).

後処理

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 16 hours
  3. customThe solvent was removed
  4. washthe residue was washed with saturated sodium bicarbonate
  5. additionwas added
  6. extractionthe mixture was extracted with EtOAc
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was chromatographed on a silica gel column
  10. washeluting with hexane:Et2O 1:2 to 0:1

出典と根拠

ORDレコード
ord-b641fc578a93489aa452d48e55ab98ba
出典データセット
uspto-grants-2000_10
特許番号
US06127386

反応ノート

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