2-Methoxyethanol → 2-Chloro-3-fluoro-5-(2-methoxyethoxy)pyridine

To a solution of 6-chloro-5-fluoro-pyridin-3-ol (CAS registry 870062-76-3) (800 mg, 5.42 mmol), 2-methoxy-ethanol (454 mg, 0.471 ml, 5.96 mmol) and triphenylphosphine (2.199 g, 8.13 mmol) in THF (40 ml) was added dropwise a solution of DIAD (1.731 g, 8.13 mmol) in THF (20 ml) while keeping the temperature at 0-5° C. The reaction mixture was stirred for 20 h at room temperature, water and brine were added and the mixture was diluted with EtOAc. The aqueous layer was twice extracted with EtOAc, the combined organic layers were dried over Na2SO4, filtered, the filtrate was concentrated and yielded after trituration with Et2O and filtration, the title compound as a white solid. The filtrate yielded another batch of the product after purification by prep. NP HPLC using an Alltech Grom Saphir 65 Si 10 μM 250×50 mm column (heptane/EtOAc, gradient 0-1.7 min 15% EtOAc, 1.7-17 min 15-100% EtOAc, 17-24.3 min 100% EtOAc, 24.3-27.8 min 0% EtOAc).

1. customat 0-5° C
2. extractionThe aqueous layer was twice extracted with EtOAc
3. dry with materialthe combined organic layers were dried over Na2SO4
4. filtrationfiltered
5. concentrationthe filtrate was concentrated
6. customyielded after trituration
7. filtrationwith Et2O and filtration
8. customThe filtrate yielded another batch of the product
9. customafter purification by prep
10. customan Alltech Grom Saphir 65 Si 10 μM 250×50 mm column (heptane/EtOAc, gradient 0-1.7 min 15% EtOAc, 1.7-17 min 15-100% EtOAc, 17-24.3 min 100% EtOAc, 24.3-27.8 min 0% EtOAc)

ORD record

ord-2000072fbf1840979c95f983ad530b72

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207164B2