3-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine → HCID 44319012, compound

HRID 1416637Notes

Reaction equation

HRID 1416637 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][Mg]Br>C1COCC1>[CH3:16][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

4

Reactant 2

HCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridineHCID 178418573HCID 178418573, compound2×

Product 1

HCID 44319012HCID 44319012, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 270 mg (1 mmol) sample of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine, from Example 28 above, was dissolved in 10 mL of THF, 3.25 mg of Ni(dppp)Cl was added, and the mixture was cooled to 0° C. To this solution was added 0.47 mL of methylmagnesium bromide, then the mixture was stirred at reflux for 20 hours. Another 0.2 mL of methylmagnesium bromide was added, and the reaction mixture was stirred for 2 hours. The reaction was quenched by addition of NH4Cl solution, and the mixture was evaporated to dryness. The residue was partitioned between H2O and CHCl3, and the organic extract was dried and concentrated.. The residue was purified by chromatography on silica gel, eluting with 5:1 chloroform:methanol, to give 120 mg of the title compound. MS (DCI/NH3) m/e: 207 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.13 (d, J=2.7 Hz, 1H), 8.05 (s, 1H), 7.03 (m, 1H), 4.04-3.89 (m, 2H), 2.66 (m, 1H), 2.48 (s, 3H), 2.32 (s, 3H), 2.35-2.26 (m, 1H), 2.09-1.98 (m, 1H), 1.92-1.68 (m, 3H).

Workup

  1. temperatureat reflux for 20 hours
  2. stirringthe reaction mixture was stirred for 2 hours
  3. customThe reaction was quenched by addition of NH4Cl solution
  4. customthe mixture was evaporated to dryness
  5. customThe residue was partitioned between H2O and CHCl3
  6. extractionthe organic extract
  7. customwas dried
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel
  10. washeluting with 5:1 chloroform

Sources & evidence

ORD record
ord-061ba7143af34cbeabcf8f417ade16e3
Source dataset
uspto-grants-1999_06
Patent number
US05914328

Reaction notes

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