Chlorosuccinimide → HCID 86707795, Verbindung

Temperatur

0 °C

To a stirred solution of 1-[4-(hydroxyimino-methyl)-phenyl]-azetidine-3-carboxylic acid methyl ester (Preparation 10, 2.36 g, 10.08 mmol) in DMF (25 mL) was added N-chloro succinimide (1.48 g, 11.09 mmol) at 0° C. Resulting reaction mixture was stirred at 0° C. for 1 hour and then at 10° C. for 1 hour. After complete consumption of starting material to chloro intermediate (red colored reaction mixture) potassium hydrogen carbonate (1.51 g, 15.12 mmol, 1.5 eq.) was added followed by of 1,2,3-trichloro-5-(1-trifluoromethyl-vinyl)benzene (1.21 g, 12.10 mmol) at room temperature. Resulting reaction mixture was stirred at room temperature for 4 hours under nitrogen atmosphere. After consumption of chloro intermediate, reaction mixture was quenched with water (200 mL) and extracted with EtOAc (2×200 mL). Combined organic layer was washed with water (2×400 mL), brine (2×200 mL), dried over anhydrous sodium sulphate and concentrated in vacuo to afford brown colored semi solid (2.5 g, crude). Crude compound was purified by column chromatography (silica gel, 100-200 mesh). Compound was eluted using 25% ethyl acetate in hexane to afford off white solid (1.91 g, 33%). 1H NMR (400 MHz, CDCl3): 3.58-3.63 (m, 2H), 3.75 (s, 3H), 4.03 (d, 1H, J=17.04 Hz), 4.07-4.15 (m, 4H), 6.39-6.42 (m, 2H), 7.46-7.49 (m, 2H), 7.63 (s, 2H); LC-MS (M+H): =506.90.

1. customResulting
2. customreaction mixture
3. waitat 10° C. for 1 hour
4. additionwas added
5. customResulting
6. customreaction mixture
7. stirringwas stirred at room temperature for 4 hours under nitrogen atmosphere
8. customAfter consumption of chloro intermediate, reaction mixture
9. customwas quenched with water (200 mL)
10. extractionextracted with EtOAc (2×200 mL)
11. washCombined organic layer was washed with water (2×400 mL), brine (2×200 mL)
12. dry with materialdried over anhydrous sodium sulphate
13. concentrationconcentrated in vacuo
14. customto afford brown colored semi solid (2.5 g, crude)
15. customCrude compound was purified by column chromatography (silica gel, 100-200 mesh)
16. washCompound was eluted

ORD-Eintrag

ord-a10d9e96aa69466280e16f03ce8476bf

Quelldatensatz

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09061013B2