Hydrochloric Acid → 3,5-Diisothiocyanatobenzoic acid

Carbon disulfide (0.54 mL, 9.1 mmol) was added to a mixture comprising 3,5-diaminobenzoic acid (0.23 g, 1.5 mmol), tetrahydrofuran (1.0 mL), water (1.0 mL) and triethylamine (0.84 mL, 6.0 mmol), followed by stirring at room temperature for 31 hours. To the obtained reaction mixture, a tetrahydrofuran (2.0 mL) solution of iodine (0.82 g, 1.6 mmol) was dropwise added over a period of 5 minutes at 0° C., followed by stirring at 0° C. for further 2.5 hours. Thereafter, 1M hydrochloric acid (1.5 mL) and sodium sulfite (76 mg, 0.30 mmol) were added and mixed. Then, ethyl acetate (6 mL) was added, and the organic layer was separated and concentrated under reduced pressure to dryness. To the obtained residue, ethyl acetate (6 mL), water (3 mL) and sodium hydrogencarbonate (10 mg, 0.12 mmol) were added, and the organic layer was concentrated under reduced pressure to dryness. To the obtained residue, chloroform (6 mL) was added and thoroughly mixed, and then an insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure to dryness, and then, to the obtained residue, chloroform (6 mL) and hexane (1 mL) were added and thoroughly mixed. Then, the insoluble matter was removed by filtration. The filtrate was concentrated under reduced pressure to dryness to obtain 3,5-diisothiocyanatobenzoic acid as a colorless solid (0.31 g, yield: 86%, HPLC purity: 97%, HPLC retention time: 5.3 min). LC-MS ES-235 (retention time: 4.6 min, condition 1).

1. customTo the obtained reaction mixture
2. stirringby stirring at 0° C. for further 2.5 hours
3. additionmixed
4. customthe organic layer was separated
5. concentrationconcentrated under reduced pressure to dryness
6. concentrationthe organic layer was concentrated under reduced pressure to dryness
7. additionTo the obtained residue, chloroform (6 mL) was added
8. additionthoroughly mixed
9. customan insoluble matter was removed by filtration
10. concentrationThe filtrate was concentrated under reduced pressure to dryness
11. additionto the obtained residue, chloroform (6 mL) and hexane (1 mL) were added
12. additionthoroughly mixed
13. customThen, the insoluble matter was removed by filtration
14. concentrationThe filtrate was concentrated under reduced pressure to dryness

ORD record

ord-f54a88d5240f4554a96059712d0a7fe3

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367857B2