4-Vinylpyridine → 3-(1-Boc-2-(s)-pyrrolidinyl-methoxy)-5-(4-pyridinyl-ethenyl)pyridine

HRID 2305159Notes

Reaction equation

HRID 2305159 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19](Br)[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:22]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)=[CH2:23].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C([O-])(O)=O.[Na+]>C(#N)C.CCN(CC)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([CH:23]=[CH:22][C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

8

Reactant 4

HCID 75024-VinylpyridineHCID 80271Tri-o-tolylphosphineHCID 516892Sodium BicarbonateHCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 540343103-(1-Boc-2-(s)-pyrrolidinyl-methoxy)-5-(4-pyridinyl-ethenyl)pyridineYield 80%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(1-BOC-2-(S)-pyrrolidinylmethoxy)-5-bromopyridine (300 mg, 0.84 mmol) in acetonitrile (10 mL) and NEt3 (1 mL) was added 4-vinylpyridine(0.15 mL, 1.34 mmol), palladium acetate (28 mg, 0.13 mmol) and tri-o-tolylphosphine (141 mg). The reaction mixture was heated in a sealed tube at 100° C. for 16 h. After cooling to room temperature, saturated NaHCO3 solution was added. The mixture was extracted with EtOAc (2×). The combined organic solvent was dried (MgSO4), concentrated and chromatographed (silica gel; hexane/EtOAc, 2:1 to 1:2) to afford an oil (255 mg, 80%): 1H NMR (CDCl3, 300 Hz) δ 1.50 (s, 9H), 1.90 (m, 1H), 2.00-2.10 (m, 2H), 3.30-3.50 (m, 2H), 4.00 (m, 1H), 4.14-4.24 (m, 2H), 4.28 (m, 1 H), 7.10 (m, 1H), 7.24 (m, 1H), 7.36-7.40 (m, 3H), 8.26 (s, 1H), 8.30 (s, 1H), 8.60 (d, 2H, J=6.5 Hz); MS (CI/NH3) m/z 382 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was extracted with EtOAc (2×)
  3. dry with materialThe combined organic solvent was dried (MgSO4)
  4. concentrationconcentrated
  5. customchromatographed (silica gel; hexane/EtOAc, 2:1 to 1:2)

Sources & evidence

ORD record
ord-0e8db0d60e12495080073bf6de34f5a7
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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