Tri-o-tolylphosphine → HCID 54009538, compound

HRID 2305164Notes

Reaction equation

HRID 2305164 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].[CH3:22][C:23]([CH3:29])([CH3:28])[CH:24]=[CH:25][CH:26]=[CH2:27].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:27]=[CH:26][CH:25]=[CH:24][C:23]([CH3:29])([CH3:28])[CH3:22])[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 1420695,5-Dimethyl-1,3-hexadieneHCID 516892Sodium BicarbonateHCID 15480235(S)-2-((5-Bromopyridin-3-yloxy)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 54009538HCID 54009538, compoundYield 75%

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 (500 mg, 1.40 mmol) in acetonitrile (15 mL) and NEt3 (3.2 mL) was added 5,5-dimethyl-hexadiene (0.5 g, 4.54 mmol), palladium acetate (35 mg, 0.16 mmol) and tri-o-tolylphosphine (175 mg). The reaction mixture was heated in a sealed tube at 100° C. for 16 h. After cooling to room temperature, saturated NaHCO3 was added. The mixture was extracted with EtOAc (2×). The combined organic layers were dried (MgSO4), concentrated and chromatographed (silica gel; hexane/EtOAc, 5:1 to 2:1) to afford an oil (403 mg, 75%): 1H NMR (CDCl3, 300 Hz) δ 1.48 (s, 9H), 1.82-1.92 (m, 2H), 2.00-2.08 (m, 2H), 3.30-3.50 (m, 2H), 3.90 (br, 1H), 4.08-4.26 (m, 2H), 5.93 (d, 1H, J=15.5 Hz), 6.15 (dd, 1H, J=10.0, 15.0 Hz), 6.42 (d, 1H, J=16.0 Hz), 6.90 (m, 1H), 8.12 (s, 2H), 8.20 (s, 1H); MS (CI/NH3) m/z 387 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-0ad8f7966c584208847ac4bfec9a5867
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

Loading…