Formic Acid → 2-(N-formylaminomethyl)-4-(3-chloropropyl)pyridine
Reaction equation
[NH2:1][CH2:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][CH2:11][Cl:12])[CH:6]=[CH:5][N:4]=1.[OH-].[NH4+].[CH:15](O)=[O:16]>>[CH:15]([NH:1][CH2:2][C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][CH2:11][Cl:12])[CH:6]=[CH:5][N:4]=1)=[O:16]Participants
Procedure
A solution of 2-aminomethyl-4-(3-chloropropyl)pyridine (0.47 g) in 1 ml of formic acid is heated at 90° for 18 hours, cooled to 0° and made basic by the addition of saturated ammonium hydroxide solution. Extraction with methylene chloride (4×10 ml), drying over sodium sulfate and evaporation yields 2-(N-formylaminomethyl)-4-(3-chloropropyl)pyridine (IR 1674 cm-1) which is heated at 90° in phosphorus oxychloride (0.75 g) for 15 hours. Excess phosphorus oxychloride is evaporated with toluene and the residue is suspended in methylene chloride (15 ml), cooled to 0° and made basic with saturated ammonium hydroxide. Extraction with methylene chloride (4×15 ml), drying over sodium sulfate and preparative thin layer chromatography (silica gel, EtOAc) of the residue yields 7-(3-chloropropyl)-imidazo[1,5-a]pyridine (Rf=0.24, EtOAc) as a gum; NMR (CDCl3) 3.58 (t, 2H), 6.42 (q, 1H), 7.21 (s, 1H), 7.32 (s, 1H), 7.88 (d, 1H), 8.07 (s, 1H).
Workup
- temperaturecooled to 0°
- extractionExtraction with methylene chloride (4×10 ml)
- dry with materialdrying over sodium sulfate and evaporation
Sources & evidence
- ORD record
- ord-e62fcac6776b4f5fa606c2d9a6893228
- Source dataset
- uspto-grants-1986_05
- Patent number
- US04588732
Reaction notes
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