Acetonitrile → HCID 53752356, compound

HRID 365813Notes

Reaction equation

HRID 365813 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.[C:16]1(C)C=CC=C[C:17]=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:38](=[O:41])(O)[O-:39].[Na+].[C:43](#N)C>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:43][O:39][C:38]([CH:16]=[CH:17][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)=[O:41]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 80271Tri-o-tolylphosphineHCID 516892Sodium BicarbonateHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 53752356HCID 53752356, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine (272.0 mg, 1.0 mmol) in acetonitrile (3.0 mL) and triethylamine (2.5 mL) was added methyl acyrate (0.360 mL, 4.0 mmol), palladium acetate (23.0 mg, 0.1 mmol) and tri-o-tolylphosphine (122.0 mg). After being heated in a sealed tube at 100° C. overnight, the resulting mixture was cooled to room temperature. A minimum amount of 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 CHCl3 /MeOH 10:1 to afford a light yellowish oil (205 mg, 74%). MS (CI/NH3) m/z 277 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.54-2.12 (m, 4H), 2.27-2.43 (m, 1H), 2.52 (s, 3H), 2.65-2.76 (m, 1H), 3.09-3.12 (m, 1H), 3.83 (s, 3H), 3.93-4.07 (m, 2H), 6.48 (d, J=16.2 Hz, 1H), 7.33 (dd, J=3.0, 2.1 Hz, 1H), 7.66 (d, J=16.2 Hz, 1H), 8.33 (d, J=3.0 Hz, 1H), 8.35 (d, J=2.1 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-eba1ac896b5a488e8b4e5737b4d1f24b
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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