3-Bromo-2-pyridinecarboxaldehyde

Dissolve 3-bromo-2-methylpyridine (258 mg, 1.5 mmol) in dioxane (5 mL) and add selenium dioxide while stirring (666 mg, 6.0 mmol), the mixture was refluxed for 48 h, allowed to cool, and the filtrate was concentrated. The residue was purified by column chromatography to give a pale yellow solid. (175 mg, 63percent yield).3-Bromopicolinaldehyde (B5.1) (0362) A mixture of 3-bromo-2-methylpyridine (5 g, 29 mmol), SeOA mixture of 3-bromo-2-methylpyridine (5 g, 2gmmol), SeQ2 (17.5 mg, ll6mmol) in dioxane (70 mL) was heated to 120°C andstirred for 18 h. The mixture was concentrated and purified by silica gel (PE:EA = 4:1)to give the title compound (3 g, 55percent) as a white solid. LC-MS: [M+H] = 188.1.A mixture of 4a (2.15 g, 6.52 mmol) and CaCO3 (1.44 g, 14.3 mmol) in water (35 mL) was heated to reflux for 79 h. The reaction mixture was extracted with EtOAc (4 x 20 mL). The combined organic layers were washed with water (60 mL), brine (60 mL) and dried over Na2SO4. Filtration and evaporation afforded crude product, which was purified by fc (4 cm, EtOAc:cyclohexane 1:10 to EtOAc:cyclohexane 1:3). 1H NMR (400 MHz, CDCl3): delta (ppm) 7.37 (dd, J = 8.1/4.5 Hz, 1H, 5-H-Py), 8.05 (dd, J = 8.1/1.4 Hz, 1H, 4-H-Py), 8.77 (dd, J = 4.5/1.4 Hz, 1H, 6-H-Py), 10.25 (s, 1H, CHO).A mixture of 3-bromo piconaldehyde (10 g, 53.8 mmol), copper sulfate (3.98 mL, 81 mmol) and (5)-2-methylpropane-2-sulfinamide (6.84 g, 56.4 mmol) in DCM (100 mL) was stirred at rt overnight. The solid was filtered off and the filtrate concentrated under vacuum. The residue thus obtained was purified by column chromatography using silica (100-200 mesh) with 20% EtOAc in n- hexane as eluent to give (S, E)-N-((3-bromopyridin-2-yl)methylene)-2- methylpropane-2-sulfinamide as yellow oil. 1H-NMR (400 MHz, CDC13): delta ppm 9.0 (s, 1H), 8.75 (d, 1H), 7.97 (d, 1H), 7.32 (t, 1H), 5.2 (d, 1H), 1.3 (s, 9H).Step-2. 3-Bromo-pyridine-2-carbaldehydeA suspension of 3-bromo-2-dibromomethyl-pyridine (10.0 g, 30.32 mmole) in morpholine (30.0 mL) was heated to 60 C for 1 h. The reaction mixture was cooled to rt and diluted with EtOAc (200 mL). The pH was adjusted to 4.0 by adding citric acid (40.0 g). The reaction mixture was then extracted with EtOAc (3 x 200 mL) and the combined organic layers were dried over Na2S04 and concentrated under reduced pressure. The residue was purified by column chromatography using silica (100-200 mesh) using 3 % EtOAc in hexane as eluent to give 3-bromo-pyridine-2-carbaldehyde. H-NMR (400 MHz, CDC13): delta10.23(s, 1H), 8.74-8.76(d, 1H), 8.02-8.04(d, 1H), 7.26-7.38(t, 1H).

Molecular Weight:186.01
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:184.94763
Monoisotopic Mass:184.94763
Topological Polar Surface Area:30
Heavy Atom Count:9
Complexity:107
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes