Acetyl chloride → (2-Chloro-pyridin-3-yl)-acetic acid methyl ester

Acetyl chloride (0.651 mL, 9.16 mmol) was added to a suspension of (2-chloropyridin-3-yl)acetic acid (I117) (1.048 g, 6.108 mmol) in MeOH (30 mL). The mixture was heated at reflux for 20 hours. The volatiles were removed in vacuo and the residue partitioned between DCM (100 mL) and sat. NaHCO3 (100 mL). The layers were separated and the aqueous layer extracted with DCM (2×100 mL). The combined organic layers were washed with brine (100 mL), dried (Na2SO4) and the solvent removed under reduced pressure to yield an oil which was purified by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.) to afford the title compound (I118) (0.863 g, 76%) as a pale yellow oil; 1H NMR (400 MHz, d6-DMSO) δ 8.34 (dd, J=4.8, 1.9 Hz, 1H), 7.88 (dd, J=7.5, 1.9 Hz, 1H), 7.43 (dd, J=7.5, 4.8 Hz, 1H), 3.86 (s, 2H), 3.65 (s, 3H). LCMS Method C: rt 5.04 min; m/z 186 [M+H]+.

1. temperatureThe mixture was heated
2. temperatureat reflux for 20 hours
3. customThe volatiles were removed in vacuo
4. customthe residue partitioned between DCM (100 mL) and sat. NaHCO3 (100 mL)
5. customThe layers were separated
6. extractionthe aqueous layer extracted with DCM (2×100 mL)
7. washThe combined organic layers were washed with brine (100 mL)
8. dry with materialdried (Na2SO4)
9. customthe solvent removed under reduced pressure
10. customto yield an oil which
11. customwas purified by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.)

ORD record

ord-1bb5aef5623c41678b7eb82566e61535

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012461B2