Chlorosuccinimide → (S)-tert-Butyl 2-(5-((pyridin-3-yloxy)methyl)isoxazol-3-yl)pyrrolidine-1-carboxylate

To a DMF (60 mL) solution of the compound (8.57 g) obtained in Example 2-(1), NCS (5.341 g) was added in small portions at 0° C. and the mixture was stirred at room temperature for an hour. The reaction mixture was cooled to 0° C. and after adding a solution of 3-(prop-2-yn-1-yloxy)pyridine (2.663 g) in THF (5 mL) and a solution of Et3N (5.6 mL) in THF (15 mL), the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was added to saturated aqueous sodium bicarbonate (200 mL), followed by extraction with AcOEt (200 mL). The resulting organic layer was washed with brine (200 mL), dried (MgSO4), filtered and concentrated to give a crude product, which was further purified by neutral silica gel chromatography (AcOEt/hexane) to give the titled compound (3.81 g, pale yellow solid.)

1. temperatureThe reaction mixture was cooled to 0° C.
2. extractionfollowed by extraction with AcOEt (200 mL)
3. washThe resulting organic layer was washed with brine (200 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customto give a crude product, which
8. customwas further purified by neutral silica gel chromatography (AcOEt/hexane)

ORD record

ord-eb8e1c3588984a42b6af5122cccf4046

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181229B2