(6-Chloro-2-pyridinyl)methanol

PREPARATION 2: Preparation of (6-chloropyridine-2-yl)-methanol6.67 g (39.0 mmol) of the compound as obtained in PREPARATION 1 was dissolved in 90 ml of anhydrous tetrahydrofuran, and then cooled to -45Manufacturing Example 52-1-1 (6-Chloro-pyridin-2-yl)-methanol; To a mixture of 2-chloro-6-methylpyridine (1.0 g, 7.84 mmol) and dichloromethane (20 mL) was added m-chloroperbenzoic acid (3.5 g, 13.2 mmol) on an ice bath, which was stirred for 1.5 hours at 40° C. Water and sodium hydrogencarbonate were added to the reaction mixture, which was then extracted with dichloromethane. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure. Acetic anhydride (20 mL) was added to the resulting residue and stirred for 1 hour at 100° C. The reaction mixture was cooled to room temperature and concentrated under a reduced pressure. A 5 N aqueous sodium hydroxide solution (4 mL, 20.1 mmol) was added to a mixture of the resulting residue and methanol (20 mL) on an ice bath, which was stirred for 30 minutes. Water was added to this mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:1) to obtain the title compound (200.0 mg, 18percent).Step 3. 6-chloro-2-hydroxymethylpyridine A solution of 2-acetoxymethyl-6-chloropyridine (17.3 g; 93.3 mmol), prepared as in step 2, in 250 mL 10% aqueous HCl was heated at reflux for 1.5 hours. The reaction mixture was cooled to room temperature and poured into 300 mL saturated aqueous sodium bicarbonate. The solution was adjusted to pH 9 by the addition of solid sodium bicarbonate. The solution was extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate and concentrated. The 6-chloro-2-hydroxymethylpyridine was used with no further purification.(iii) 6-Chloro-2-pyridylmethanol Hydrolysis of the product obtained in Part (ii) in 10 ml 2N hydrochloric acid at 70 C. for one hour, followed by neutralization (K2CO3), extraction with chloroform and evaporation of solvent from the dried extract gave 1.87 g of crude alcohol which was purified by column chromatography on silica gel to yield 0.982 g pure material. 1H-NMR(CDCl3)ppm (delta): 4.8 (s, 2H), 5.3 (bs, 1H), 7.0-7.8 (m, 3H).(iii) 6-Chloro-2-pyridylmethanol Hydrolysis of the product obtained in Part (ii) in 10 ml 2N hydrochloric acid at 70 C. for one hour, followed by neutralization (K2 CO3), extraction with chloroform and evaporation of solvent from the desired extract gave 1.87 g of crude alcohol which was purified by column chromatography on silica gel to yield 0.982 g pure material. 1 H--NMR(CDCl3)ppm (delta): 4.8 (s, 2H), 5.3 (bs, 1H), 7.0-7.8 (m, 3H).Compounds 6-chloro-2-hydroxymethyl pyridine 1 b (1.50 g, 10.5 mmol) was mixed with 12 methylamine (15 mL, 30% solution in 8 ethanol), and stirred for 48 h at 100 C. The mixture was cooled to room temperature and subjected to exsolution under reduced pressure. The residuals were purified through silica gel column chromatography (petroleum ether/ethyl acetate 10:1 to 1:2), to obtain a target 13 product (6-(methylamino) pyrid-2-yl) methanol 1c (0.70 g, yellow oil), at a yield of 48%. (0125) MS m/z (ESI): 139 [M+1].

Molecular Weight:143.57
XLogP3:1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:143.0137915
Monoisotopic Mass:143.0137915
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes