Formaldehyde formic acid → 4-Methyl-3-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

HRID 617319Notes

Reaction equation

HRID 617319 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][NH:11]1.[CH:15](O)=O.C=O>>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[CH3:15]

Participants

3

Reactant 2

HCID 18761834Formaldehyde formic acidHCID 21309703HCID 21309703, compound

Product 1

HCID 100817314-Methyl-3-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Procedure

To a 330 mg sample of 4-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine (from Example 27 above) was added a solution of formic acid/formaldehyde (1:2, 2 mL). The mixture was heated at reflux for 5 hours, and the volatiles were removed by evaporation. The residue was dissolved in 1 mL of 20% NaOH. The solution was extracted with CH2Cl2 (3×), then the organic layer was dried (Na2SO4) and concentrated. The crude product was purified by chromatography over silica gel to afford 295 mg of the title compound. MS (DCI/NH3) m/e: 207 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.17 (s, 1H), 8.12 (d, J=5.5 Hz, 1H), 7.06 (d, J=5.5 Hz, 1H), 4.07 (dd, J=3.3, 10.6 Hz, 1H), 3.98 (dd, J=7.4, 10.6 Hz, 1H), 3.15-3.08 (m, 1H), 2.76-2.68 (m, 1H), 2.53 (s, 3H), 2.38-2.25 (m, 1H), 2.26 (s, 3H), 2.12-1.67 (m, 4H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 hours
  3. customthe volatiles were removed by evaporation
  4. dissolutionThe residue was dissolved in 1 mL of 20% NaOH
  5. extractionThe solution was extracted with CH2Cl2 (3×)
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography over silica gel

Sources & evidence

ORD record
ord-e9a7f44ace9846c28775c5ff55c48ced
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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