Formaldehyde formic acid → 4-methyl-3-((1-methyl-2-(S)-pyrrolidinyl)methoxy)pyridine dihydrochloride
Reaction equation
[ClH:1].Cl.[CH3:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[O:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][NH:13]1.[CH:17](O)=O.C=O>>[ClH:1].[ClH:1].[CH3:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][C:5]=1[O:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17]Participants
Procedure
To a 330 mg sample of 4methyl-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 (3X), 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
- temperatureThe mixture was heated
- temperatureat reflux for 5 hours
- customthe volatiles were removed by evaporation
- dissolutionThe residue was dissolved in 1 mL of 20% NaOH
- extractionThe solution was extracted with CH2Cl2 (3X)
- dry with materialthe organic layer was dried (Na2SO4)
- concentrationconcentrated
- customThe crude product was purified by chromatography over silica gel
Sources & evidence
- ORD record
- ord-dd788ce24ee74b5fa2908fdbe7b25643
- Source dataset
- uspto-grants-1999_06
- Patent number
- US05914328
Reaction notes
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