4-Bromo-2-ethylpyridine

Preparation 24; 4-Bromo-2-ethyl-pyridinePrepare the title compound according to the general procedure described in Journal Organic Chemistry, Vol. 50, No. 22, 1985, page 4410-4411. Slurry 4- bromopyridine hydrochloride (4.17 g, 0.021 mol) in THF (100 mL) and cool to -78 A mixture of 2-ethyl-4-nitro-pyridine (2.3g, 15. 1mmol) and acetyl bromide (9 mL) were heated together at 75 C for 16 hours. More acetyl bromide (10 mL) was added and the reaction was heated to 100 C for 5 hrs. The reaction mixture was poured into ice, made basic with 20percent NAOH and extracted with EtOAc. The organic extracts were washed with brine, dried over NA2SO4 and concentrated to a black oil. Purification by flash silica gel chromatography (0percent to 25percent EtOAc) gave the product as an oil (1.72g, 62percent). 1H NMR (400 MHz, CDCI3) : 6 1.30 (t, J=7.6 Hz, 3 H), 2.81 (d, J=7.6 Hz, 2 H), 7.28 (dd, J=5.3, 1.8 Hz, 1 H), 7.35 (d, J=1.8 Hz, 1 H), 8.34 (d, J=5.3 Hz, 1 H).(a) 4-Bromo-2-ethylpyridine 4-Amino-2-ethylpyridine (18 g) was dissolved with warming in 48 ml of 48% hydrogen bromide. The solution was cooled to 0 C. and 15 ml of bromine was added dropwise followed by a solution of 25.4 g of sodium nitrite in 37 ml of water over 1/2 hour while maintaining the temperature below 5 C. The mixture was allowed to warm to room temperature over 2 hours and was then poured onto ice and made alkaline with 35% sodium hydroxide. The aqueous mixture was extracted three times with 200 ml of methylene chloride, the extract was concentrated and the residue was taken up in diethyl ether. The ether solution was dried over magnesium sulfate and concentrated in vacuo at below 40 C. to give, after chromatography (silica gel; 70:30 hexane-ether), 4.1 g of the title compound as an orange oil.Preparation 24; 4-Bromo-2-ethyl-pyridinePrepare the title compound according to the general procedure described in Journal Organic Chemistry, Vol. 50, No. 22, 1985, page 4410-4411. Slurry 4- bromopyridine hydrochloride (4.17 g, 0.021 mol) in THF (100 mL) and cool to -78 0C under nitrogen. Add ethylmagnesium bromide (15.7 mL of a 3.0 M solution in diethyl ether, 2.2 equiv.) dropwise via syringe. Stir the reaction at -78 0C for 10 minutes then remove the ice bath and allow the reaction to warm to room temperature. Quench reaction with 20% ammonium chloride (aq) then dilute with diethyl ether. Wash organics with water, 1 N HCl (aq), then aqueous saturated sodium chloride. Dry organics over magnesium sulfate, filter and concentrate in vacuo. Redissolve the residue in toluene (100 mL) and place under nitrogen. Dissolve tetrachloro-l, 2-benzoquinone (5.8 g, 1.1 equiv.) in acetic acid (50 mL) and add dropwise to the reaction. Allow reaction to stir overnight at room temperature. Make the mixture basic by adding 1 N NaOH (aq) then extract with ethyl acetate. Acidify organic layer with 1 N HCl (aq) and extract with ethyl acetate. Set organics aside. Basify the aqueous layer with 1 N NaOH (aq) and extract with DCM. Wash this organic layer with aqueous saturated sodium chloride then dry over magnesium sulfate. Filter and concentrate in vacuo to give a brown residue (2.64 g, 66%). LCMS (ES), m/z 188 (M+l, bromide pattern).A mixture of 2-ethyl-4-nitro-pyridine (2.3g, 15. 1mmol) and acetyl bromide (9 mL) were heated together at 75 C for 16 hours. More acetyl bromide (10 mL) was added and the reaction was heated to 100 C for 5 hrs. The reaction mixture was poured into ice, made basic with 20% NAOH and extracted with EtOAc. The organic extracts were washed with brine, dried over NA2SO4 and concentrated to a black oil. Purification by flash silica gel chromatography (0% to 25% EtOAc) gave the product as an oil (1.72g, 62%). 1H NMR (400 MHz, CDCI3) : 6 1.30 (t, J=7.6 Hz, 3 H), 2.81 (d, J=7.6 Hz, 2 H), 7.28 (dd, J=5.3, 1.8 Hz, 1 H), 7.35 (d, J=1.8 Hz, 1 H), 8.34 (d, J=5.3 Hz, 1 H).

Molecular Weight:186.05
XLogP3:2.3
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:184.98401
Monoisotopic Mass:184.98401
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:85
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes