Thiophosgene → N-(2-fluoro-6-isopropylphenyl)hydrazinecarbothioamide

To a 100 mL round-bottomed flask equipped with a stir bar and nitrogen inlet were added 2-fluoro-6-isopropylaniline (0.415 g, 2.71 mmol), dichloromethane (13.6 mL), water (6.78 mL), and sodium bicarbonate (0.683 g, 8.13 mmol). To this biphasic mixture was added thiophosgene (0.199 mL, 2.60 mmol) and the reaction was stirred vigorously for 2 hours. The suspension was filtered through a phase separator cartridge and the organic phase was concentrated in a 100 mL round-bottomed flask. The flask was equipped with a magnetic stir bar and nitrogen inlet and the residue was dissolved in ethanol (6.78 mL). To the resulting solution was added hydrazine hydrate (0.131 mL, 2.71 mmol) and the reaction was stirred at room temperature for 2 days. The solution was concentrated and the resulting residue was suspended in a mixture of diethyl ether and hexanes and reconcentrated to give a solid. The solid was suspended in a minimal amount of diethyl ether and the mixture was diluted with hexanes. The majority of the diethyl ether was evaporated and the resulting solid was collected by vacuum filtration, washed with hexanes and then dried under house vacuum to provide the title compound (0.518 g, 2.28 mmol, 84% yield) as a white solid: mp 122-124° C.; 1H NMR (400 MHz, CDCl3) δ 8.56 (bs, 1H), 7.52 (bs, 1H), 7.32 (td, J=8.1, 5.6 Hz, 1H), 7.17-7.12 (m, 1H), 7.00 (ddd, J=9.5, 8.2, 1.4 Hz, 1H), 4.07 (bs, 2H), 3.15 (hept, J=7.0 Hz, 1H), 1.24 (d, J=6.9 Hz, 6H); ESIMS m/z 229 ([M+H]+).

1. customTo a 100 mL round-bottomed flask equipped with a stir bar and nitrogen inlet
2. filtrationThe suspension was filtered through a phase separator cartridge
3. concentrationthe organic phase was concentrated in a 100 mL round-bottomed flask
4. customThe flask was equipped with a magnetic stir bar and nitrogen inlet
5. dissolutionthe residue was dissolved in ethanol (6.78 mL)
6. stirringthe reaction was stirred at room temperature for 2 days
7. concentrationThe solution was concentrated
8. additionthe resulting residue was suspended in a mixture of diethyl ether and hexanes
9. customto give a solid
10. customThe majority of the diethyl ether was evaporated
11. filtrationthe resulting solid was collected by vacuum filtration
12. washwashed with hexanes
13. customdried under house vacuum

ORD record

ord-e1cfabd97c22459e8272d31838aa33c9

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018388B2