6-Bromo-3-hydroxy-2-methylpyridine

Step 2: 6-Bromo-2-methylpyridin-3-ol[00395] 4, 6-Dibromo-2-methylpyridin-3-ol (15.8 g, 59.4 mmol) was dissolved inTHF (200 mL). The solution was cooled to -78°C and n-BuLi (50 mL, 125 mmol, 2.5 M in hexane) was added drop-wise keeping the temperature at -78°C. The mixture was allowed to stir at that temperature for 2 h. The mixture was quenched with water (50 mL) and was neutralized with 2 N HCl. The aqueous mixture was extracted with dichloromethane (2x). The combined organic layers were dried (Na[00386] Step 2:[00387] 4, 6~Dibromo-2-methylpyridin-3-ol (15.8 g, 59.4 mmol) was dissolved in THF (200 mL). The solution was cooled to -78 °C and n-BuLi (50 mL, 125 mmol, 2.5 M in hexane) was added dropwise keeping the temperature below -78 °C. The reaction mixture was allowed to stir at that temperature for 2 hours. The reaction mixture was quenched with water (50 mL) and was neutralized with 2 N HC1. The aqueous mixture was extracted with dichloromethane (2 times). The combined organic layers were dried (Na4, 6-Dibromo-2-methylpyridin-3-ol (15.8 g, 59.4 mmol) was dissolved in THF (200 mL). The solution was cooled to -78° C. and n-BuLi (50 mL, 125 mmol, 2.5 M in hexane) was added drop-wise keeping the temperature below -78° C. The mixture was allowed to stir at that temperature for 2 h. The mixture was quenched with water (50 mL) and was neutralized with 2 N HCl. The aqueous mixture was extracted with dichloromethane (2×). The combined organic layers were dried (Na4, 6-Dibromo-2-methylpyridin-3-ol (15.8 g, 59.4 mmol) was dissolved in THF (200 mL). The solution was cooled to -78°C and n-BuLi (50 mL, 125 mmol, 2.5 M in hexane) was added drop-wise keeping the temperature below -78°C. The mixture was allowed to stir at that temperature for 2 h. The mixture was quenched with water (50 mL) and was neutralized with 2 N HCl. The aqueous mixture was extracted with dichloromethane (2x). The combined organic layers were dried (NaTo a solution of 4, 6-dibromo-2-methylpyridin-3-ol (1.0g) in THF (20 mL) was added at -78°C 1.6M nBuLi in hexane (4.7 mL). The reaction was stirred for 2h. Water was added (9 mL) and the reaction mixture was allowed to warm up to rt. The reaction mixture was diluted with sat. aq. NHReference Production Example 31 (0643) To a mixture of 10.8 g of 2, 4-dibromo-3-hydroxy-6-methylpyridine 30A mentioned in Reference Production Example 30 and 150 ml of tetrahydrofuran, 50.6 ml of a 1.64M n-butyllithium-hexane solution was added at −78° C., followed by stirring for 2 hours. After pouring 100 ml of water into the mixture, the mixture was acidified by adding 10percent hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue thus obtained was washed with hexane, dried under reduced pressure to obtain 6.2 g of 2-bromo-5-hydroxy-6-methylpyridine (hereinafter referred to as 31A). (0644) To a solution of 4, 6-dibromo-2-methylpyridin-3-ol (1.0g) in THF (20ml) was added at -78°C 1.6M nBuLi in hexane (4.7ml). The reaction was stirred for 2h. Water was added (9ml)and the reaction mixture was allowed to warm up to rt. The reaction mixture was diluted with sat. aq. NH4CI and EA. The layers were separated, the aq. phase was washed with EA and the combined org. layers were dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 20g cartridge, solvent A: DCM , solvent B: 7N NH3 in MeOH, gradient in percentB: 1 to 3, flow rate: 10 ml/min) to afford 550mg of a colourless solid. LC-MS (A): tR = 0.58min; [M+H]+: 188.03.Preparation 26; 6-Bromo-2-methvl-pvridin-3-ol; A solution of bromine (24.9g, 0. 47mol) in 0.5M sodium hydroxide solution (175mL). was added dropwise to an ice cooled solution of 2-methyl-3-pyridinol (11. 4g, 0. 104mol) in 0.5M sodium hydroxide solution (175mL). After standing for 24 hours, the solution was acidified to pH7 with concentrated hydrochloric acid and the mixture was stirred for 18 hours. The reaction mixture was then filtered off and the residue was stirred in dichloromethane for 1 hour. The precipitate that formed was filtered off to give the title product as a solid in 20percent yield (3.83g). 'H NMR (DMSO-D6, 400MHz) zu : 2.15 (s, 3H), 7.15 (d, 1H), 7.20 (d, 1H), 10.1 (s, 1H) MS APCI+ m/z 188 [MH] +

Molecular Weight:188.02
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:186.96328
Monoisotopic Mass:186.96328
Topological Polar Surface Area:33.1
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes