Iodoform → 7-Bromo-4-[1-iodomethylidene]-1,2,3,4-tetrahydro-[1,8]naphthyridine
Reaction equation
[Br:1][C:2]1[N:11]=[C:10]2[C:5]([C:6](=O)[CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1.[CH:13](I)(I)[I:14]>O1CCCC1.C(Cl)Cl>[Br:1][C:2]1[N:11]=[C:10]2[C:5]([C:6](=[CH:13][I:14])[CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1Participants
Procedure
To a suspension of 7-bromo-2,3-dihydro-1H-[1,8]naphthyridin-4-one (1.5 g) in anhydrous tetrahydrofuran (195 mL) was added a solution of CrCl2 (6.79 g, 8.35 eq) and CHI3 (5.55 g, 2.13 eq) in anhydrous tetrahydrofuran (66 mL). The reaction was stirred at room temperature for 16 hours, diluted with methylene chloride (300 mL), and then washed with saturated NaHCO3 (300 mL). The aqueous phase was extracted twice with methylene chloride (100 mL) and the combined organic layers were washed with brine and then dried over Na2SO4. The solution was filtered and concentrated under reduced pressure. Silica gel chromatography using a gradient of 0-30% ethyl acetate/hexane as the eluting solvent gave the title compound as a yellow solid (27% yield). Alkene geometry was determined by nOe. LCMS: m/z=352 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.69 (t, J=6.0 Hz, 2H), 3.43-3.51 (m, 2H), 5.25 (bs, 1H), 6.23 (s, 1H), 6.74 (d, J=8.0 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H).
Workup
- washwashed with saturated NaHCO3 (300 mL)
- extractionThe aqueous phase was extracted twice with methylene chloride (100 mL)
- washthe combined organic layers were washed with brine
- dry with materialdried over Na2SO4
- filtrationThe solution was filtered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-060914da9fae4337922438b9cb049f4c
- Source dataset
- uspto-grants-2009_10
- Patent number
- US07601716B2
Reaction notes
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