3,5-Dichloropyridine → HCID 118342944、化合物

To a solution of 3,5-dichloropyridine (1.069 g, 7.22 mmol) in THF (12.04 ml) at −78° C. was added lithium diisopropylamide, 2.0 M heptane/THF/ethylbenzene (4.57 ml, 9.15 mmol) dropwise. After stirring for 1 h, a solution of (R)-5,5-diallyltetrahydro-3H-pyrrolo[1,2-c][1,2,3]oxathiazole 1,1-dioxide (1.172 g, 4.82 mmol) in THF (10 mL) was added dropwise at −78° C. and the mixture was allowed to warm to room temperature with stirring for 6 h. After evaporating of the solvent, the resulting beige foam was treated with hot 2 N HCl (12 ml) and EtOH (12 ml) overnight. The mixture was cooled to room temperature and basified with 1 N NaOH and extracted with EtOAc. The extracts were dried, evaporated and purified by chromatography through a REDISEP™ pre-packed silica gel column (40 g), eluting with a gradient of 1% to 6% MeOH in DCM, to provide (R)-3,5-dichloro-4-((4,4-diallylpyrrolidin-2-yl)methyl)pyridine (0.70 g, 2.249 mmol, 46.7% yield) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.46 (s, 2H), 5.66-5.86 (m, 2H), 5.03-5.18 (m, 4H), 3.59-3.72 (m, 1H), 3.25 (d, J=7.15 Hz, 1H), 2.97 (d, J=11.51 Hz, 1H), 2.82 (d, J=11.51 Hz, 1H), 2.10-2.28 (m, 4H), 1.78 (dd, J=13.06, 6.95 Hz, 1H), 1.51-1.61 (m, 1H); LCMS (ESI) m/z 311.0 (M+H)+.

1. stirringwith stirring for 6 h
2. customAfter evaporating of the solvent
3. additionthe resulting beige foam was treated with hot 2 N HCl (12 ml) and EtOH (12 ml) overnight
4. temperatureThe mixture was cooled to room temperature and basified with 1 N NaOH
5. extractionextracted with EtOAc
6. customThe extracts were dried
7. customevaporated
8. custompurified by chromatography through a REDISEP™ pre-packed silica gel column (40 g)
9. washeluting with a gradient of 1% to 6% MeOH in DCM

ORDレコード

ord-2152ecede9524b5d89849c22394e2444

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09365522B2