Picolinic acid → tert-Butyl 4-chloropicolinate

To thionyl chloride (40 mL) was added picolinic acid (10.5 g, 85.4 mmol) followed by sodium bromide (0.93 mg, 9.2 mmol) at room temperature. The reaction mixture was refluxed for 24 h. the reaction mixture was then cooled to room temperature and thionyl chloride was removed in vacuo. The residue was diluted with THF (50 mL) and concentrated to dryness. The compound was used for further reaction without purification. To a solution of t-butanol (19.6 mL), pyridine (20.7 mL) and 1,2-dichloroethane (80 mL) at 0° C., was added a solution of 4-chloropicolinyl chloride above in 1,2-dichloroethane (60 mL). The reaction mixture was heated at 50° C. for 24 h. The reaction mixture was diluted with DCM and then washed with 5% citric acid several times. The organic layer was dried over MgSO4 and concentrated. The residue was purified by column chromatography (30% EtOAc in hexanes) to give a colorless oil (6.6 g, 60.4%). 1H NMR (DMSO-d6): δ 8.68 (d, J=5 Hz, 1H), 8.01 (d, J=2 Hz, 1H), 7.79 (dd, J=5 and 2 Hz, 1H), 1.56 (s, 9H).

1. temperatureThe reaction mixture was refluxed for 24 h. the reaction mixture
2. customthionyl chloride was removed in vacuo
3. additionThe residue was diluted with THF (50 mL)
4. concentrationconcentrated to dryness
5. customThe compound was used for further reaction without purification
6. temperatureThe reaction mixture was heated at 50° C. for 24 h
7. washwashed with 5% citric acid several times
8. dry with materialThe organic layer was dried over MgSO4
9. concentrationconcentrated
10. customThe residue was purified by column chromatography (30% EtOAc in hexanes)

ORD record

ord-d2b5d55bb6394d7e982cc2e4b48a35e9

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029401B2