Phosphorus oxychloride → HCID 43805572, compound

Temperature

78 °C

A stirred mixture of 4-bromo-2-chlorobenzoic acid (2 g, 8.49 mmol) and hydrazinecarbothioamide (1.161 g, 12.74 mmol) was cooled under nitrogen in an ice-bath. POCl3 (2.375 mL, 25.5 mmol) was then added dropwise. On completion of addition, the reaction mixture was warmed to 78° C. and left to stir for 3 hours. The reaction mixture was allowed to cool to room temperature then cooled further in an ice-bath. Quenching by addition of ice-water (50 mL) resulted in a solid/gum-like mass. This material was sonicated for 1.5 hours and the resulting suspension was diluted with a further 50 mL water and slurried for 16 hours. The suspension was filtered under vacuum and the solid rinsed with water, then re-suspended in saturated NaHCO3(aq) (100 mL). The suspension was slurried for 30 minutes then filtered under vacuum and rinsed with water to afford the crude product as an off-white solid. The crude product was pre-absorbed onto silica gel and purified by flash chromatography using a gradient from 0-10% MeOH/DCM over 30 minutes to afford the title compound as a pale yellow/off-white solid (1.087 g, 44% yield). LC-MS: Rt 1.09 min; MS m/z 292.0 [M+2H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.96 (d, J=8.59 Hz, 1H), 7.91 (d, J=2.02 Hz, 1H), 7.68 (dd, J=8.59, 2.02 Hz, 1H), 7.51 (s, 2H).

1. temperaturewas cooled under nitrogen in an ice-bath
2. additionOn completion of addition
3. waitleft
4. temperatureto cool to room temperature
5. temperaturethen cooled further in an ice-bath
6. customQuenching by addition of ice-water (50 mL)
7. customresulted in a solid/gum-like mass
8. customThis material was sonicated for 1.5 hours
9. waitslurried for 16 hours
10. filtrationThe suspension was filtered under vacuum
11. washthe solid rinsed with water
12. waitThe suspension was slurried for 30 minutes
13. filtrationthen filtered under vacuum
14. washrinsed with water
15. customto afford the crude product as an off-white solid
16. customThe crude product was pre-absorbed onto silica gel
17. custompurified by flash chromatography
18. customover 30 minutes

ORD record

ord-ad7a922693e748db99418d60fc9a3ad3

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040712B2