2-(6-broMopyridin-2-yl)propan-2-ol

Place a 1.6 M solution of n-butyl lithium in hexane (31.2 niL, 50 mmol) in a dry 250 rnL round bottomed flask fitted with a stir bar, septum and temperature probe. Cool in a dry- ice acetone bath to -76 Step 1 Step 1 2-(6-Bromopyridin-2-yl)propan-2-ol A dry 250 mL round bottomed flask fitted with a stir bar and septum was charged with n- buthyllithium 1.6 M in hexane (30.3 mL, 48.5 mmol), the flask was cooled in a dry- ice acetone bath to -76 °C then THF (30 mL) was added followed by a solution of 2, 6-dibromopyridine (11.5 g, 48.5 mmol) in THF (60 mL) slowly via cannula over 15 min. The dark yellow-brown solution was stirred for 30 minutes in the dry- ice bath, then propan-2-one (4.75 g, 6 mL, 81.7 mmol) was added. The deep green solution was stirred in the dry- ice bath for 15 minutes then was warmed to room temperature over 1 hour. A saturated aqueous solution of ammonium chloride (100 mL) was carefully added and the mixture extracted with dichloromethane (3 x 200 mL). The combined organic extracts were dried over magnesium sulfate then concentrated in vacuo and purified by chromatography (silica gel 50 μιη, 150g, Analogix, eluting with 0 to 50percent dichloromethane in hexanes) to obtain 2-(6-bromopyridin-2-yl)propan-2-ol (9.9 g, 94 percent) as a light yellow, clear liquid. 1H NMR (CHLOROFORM-d) δ: 7.52 - 7.59 (m, 1H), 7.33 - 7.40 (m, 2H), 4.05 (br. s., 1H), 1.55 (s, 6H); MS (EI/CI) m/z: 216.1, 218.1 [M + H].Preparation 31 To a solution of l-(6-bromo-pyridin-2-yl)-ethanone (4.0 g, 20 mmol) in anhydrous THF (50 mL) at 0 °C was added a solution of methyl magnesium bromide (3.0 M, 8.0 mL, 24 mmol, 1.2 eq) in THF dropwise over 20 min. The mixture was stirred at rt for 16 h, quenched with HMethylmagnesium iodide (3M in Et20, 1.50 ml, 4.48 mmol) was added to a solution of methyl 6-bromopyridine-2- carboxylate (0.430 g, 1.99 mmol) in dry Et20 (1 5 ml) under N2. After 5 min at RT the reaction was quenched with 1 M HCI (10 ml) and extracted with EtOAc (15 ml). The organic extract was washed with sat. NaHC03 solution (1 5 ml) and brine (10 ml), dried (MgS04) and concentrated in vacuo. The desired product was obtained as a yellow oil (0.365 g, 1.69 mmol, 85percent). Rf 0.60 (1 :1 Hexane:EtOAc); I R (cm-1 ) 3420, 2975, 2930, 1731 , 1701 , 1 580, 1 553; 1 H NMR (400 MHz, DMSO-d6) 1.42 (6H, s, C(CH2)2), 5.33 (1 H, s, OH), 7.47 (1 H, dd, J = 7.7, 0.9 Hz, H-5), 7.67 (1 H, dd, J = 7.7, 0.9 Hz, H-3), 7.73 (1 H, dd, J = 7.7, 7.7 Hz, H-4); 13C N MR (125 MHz, DMSO-d6) 30.9 (C(CH2)2), 72.6 (C(CH2)2), 1 18.5 (Ar-C), 126.0 (Ar-C), 140.4 (Ar-C), 140.5 (Ar-C), 170.8 (Ar-C).

Molecular Weight:216.07
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:214.99458
Monoisotopic Mass:214.99458
Topological Polar Surface Area:33.1
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes