Tri-o-tolylphosphine → HCID 54360554, compound

HRID 2305096Notes

Reaction equation

HRID 2305096 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1.[CH3:16][C:17]([CH3:23])([CH3:22])[CH:18]=[CH:19][CH:20]=[CH2:21].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)(O)[O-].[Na+]>C(#N)C.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:16][C:17]([CH3:23])([CH3:22])[CH:18]=[CH:19][CH:20]=[CH:21][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 1420695,5-Dimethyl-1,3-hexadieneHCID 516892Sodium BicarbonateHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 54360554HCID 54360554, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine (272 mg, 3.0 mmol) in acetonitrile (3.0 mL) and triethylamine (2.5 mL) was added 5,5-dimethyl-1,3-hexadiene (0.50 mL), palladium acetate (23.0 mg, 0.1 mmol) and tri-o-tolylphosphine (122 mg, 0.1 mmol). After being heated in a sealed tube at 100° C. overnight, the resulting mixture was cooled to room temperature. Minimum amount of saturated sodium bicarbonate was added to free the amine hydrochloride salt, and the mixture was extracted with EtOAc, dried (MgSO4), and concentrated. The residue was chromatographed on a silica gel column, eluting with CHCl3/MeOH 10:1 to afford a light yellowish oil (225 mg, 75%). MS (CI/NH3) m/z 301 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.08 (S, 9H), 1.55-1.77 (m, 3H), 1.98-2.10 (m, 1H), 2.37-2.47 (m, 1H), 2.50 (s, 3H), 2.64-2.73 (m, 1H), 3.07-3.17 (m, 1H), 3.90-4.06 (m, 2H), 5.93 (d, J=15.5 Hz, 1H), 6.16 (dd, J=15.5, 9.9 Hz, 1H), 6.42 (d, J=15.5 Hz, 1H), 6.78 (dd, J=9.9, 15.5 Hz, 1H), 7.21 (dd, J=3.0, 1.5 Hz, 1H), 8.14 (d, J=3.0 Hz, 1H), 8.19 (d, J=1.5 Hz, 1H).

Workup

  1. temperaturethe resulting mixture was cooled to room temperature
  2. extractionthe mixture was extracted with EtOAc
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was chromatographed on a silica gel column
  6. washeluting with CHCl3/MeOH 10:1

Sources & evidence

ORD record
ord-6f30969d01734628b41c723a6c69169a
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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