2-Chloro-3-pyridineacetic acid

A solution of 15percent w/w NaOH (15 mL) was added to (2-chloropyridin-3-yl)acetonitrile (1116) (0.932 g, 6.1 mmol). The mixture was heated at reflux for 35 minutes then cooled to room temperature. The mixture was further cooled to 0 °C and then acidified with cone. HCI (ca 5 mL) to pH 1. The suspension was left to stand for 1 hour in an ice bath. The precipitate was filtered and washed with cold propan-2-ol (3x15 mL) to yield the title compound (1117) (1 .05 g, 100percent) as an off-white solid; A solution of 15percent w/w NaOH (15 mL) was added to (2-chioropyridin-3-yl)acetonitrile (1116) (0.932 g, 6.11 mmol). The mixture was heated at reflux for 35 minutes then cooled to room temperature. The mixture was further cooled to 0 °C and then acidified with cone. HCi (ca 5 mL) to pH 1. The suspension was left to stand for 1 hour in an ice bath. The precipitate was filtered and washed with cold propan-2~ol (3x15 mL) to yield the title compound (1117) (1.05 g, 100percent) as an off-white solid; (2-Chloropyridin-3-yl)acetic acidTo a 2 L reactor, set for reflux, was stirred a pre-prepared 15percent w/w solution of sodium hydroxide (5 vols) to which was added (2-chloropyridin-3-yl)acetonitrile (Intermediate 2\ 276.4 g, 1.81M). The beige suspension was heated to reflux for 30 minutes, at which point the reaction was deemed complete by HPLC. The brown solution was then cooled to 0-50C and acidified to pH 1 with cone. HCl while keeping the temperature below 1O C, using concentrated hydrochloric acid (1.8 vols). An off-white solid precipitated and was left to mature for another hour before filtration. Once dried, the material was recrystallised from propan-2-ol (4 vols) to afford the title compound as an off-white material in excellent yield and purity (280.3 g, 90percent). 'H (d?-DMSO, 300 MHz) 12.70 (IH, s), 8.35 (IH, dd), 7.85 (IH, dd), 7.40 (IH, dd), 4.25 (2H, s). LCMS (ES)+ RT 1.75 min, m/e 171.99 (M+l, Product).(2-Chloropyridin-3-yl)acetic acid To a 2 L reactor, set for reflux, was stirred a pre-prepared 15percent w/w solution of sodium hydroxide (5 vols) to which was added (2-chloropyridin-3-yl)acetonitrile (Intermediate 2; 276.4 g, 1.81M). The beige suspension was heated to reflux for 30 minutes, at which point the reaction was deemed complete by HPLC. The brown solution was then cooled to 0-5INTERMEDIATE 3(2-Chloropyridin-3-yl)acetic acidTo a 2 L reactor, set for reflux, was stirred a pre-prepared 15percent w/w solution of sodium hydroxide (5 vols) to which was added (2-chloropyridin-3-yl)acetonitrile {Intermediate 2; 216 A g, 1.81M). The beige suspension was heated to reflux for 30 minutes, at which point the reaction was deemed complete by HPLC. The brown solution was then cooled to 0-5(Step 4) (2-Chloropyridin-3-yl)acetonitrile (1.0 g, 6.55 mmol) in conc. hydrochloric acid (15 mL) is stirred at 100° C. for 2 hr. After cooling to room temperature the reaction mixture is diluted with water and the solution is concentrated to dryness. The residue is dissolved in water, made basic with ammonium hydroxide, re-acidified with acetic acid and extracted with ethyl acetate. The combined extract is washed with brine, dried, filtered and concentrated to give (2-chloropyridin-3-yl)acetic acid (442 mg, 39percent) as a white solid.NaCN (1.3 mol) was dissolved in water (100 g) and 202 g of ethanol and 1 g of the polymerization inhibitor hydroquinone were added, When the temperature was raised to 60 ° C, 2-chloro-3-chloromethylpyridine (total amount 1 mol) was added in batches, and the mixture was heated to 70The reaction was carried out for 2-3 hours (central control). After completion of the reaction, the reaction mixture was dehydrated and eluted with water, and water (330 g) was added dropwise with NaOH (1.3 mol)(30percent), dropping at 50 for 15min, after the drop in the temperature of the reaction at this temperature 30min, after the temperature to 80 to the anti-Should be completed (in control), micro-negative pressure deamination, ammonia after completion (removal of ammonia is about 150g), cooling, plus activated carbon release polymer(Decolorization), filtration, the filtrate dropwise hydrochloric acid acid (pH 3-4), cooling and filtration, The solid 2-chloro-3-pyridineacetic acid (CAS: 61494-55-1) was washed with water, Vacuum drying 157.8 g, The quantitative content of HPLC was 99.5percent and the yield was 92.1percent.

Molecular Weight:171.58
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:171.0087061
Monoisotopic Mass:171.0087061
Topological Polar Surface Area:50.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes