Sulfuric Acid → HCID 71061950, compound

Temperature

50 °C

Sulfur (0.91 g; 27.5 mmol) was added portions wise to a stirred 0.5M solution of bromo-(cyclopropyl)magnesium in THF (50.0 ml; 25.0 mmol). The batch was stirred at 50° C. for 1 hour and then cooled to 0° C. Lithium tetrahydridoaluminate(1-) (522 mg; 13.8 mmol) was cautiously added under stirring. The batch was stirred for 30 minutes at 50° C. and cooled to 0° C. again. Water (2 ml) was cautiously added under stirring. Finally, sulfuric acid (5%; 100 ml) was cautiously added and the batch was stirred for 10 minutes. The organic phase was separated and the aqueous phase was extracted with diethyl ether (2×). The combined organic phases were washed with saturated aqueous ammonium chloride solution (2×), aqueous sodium bicarbonate solution (5%, 2×), water (2×) and saturated aqueous sodium chloride solution (2×). The organic phase was dried (magnesium sulfate) and filtered before it was slowly added to a stirred batch of 1-(chloromethyl)-3-nitrobenzene (2.15 g; 12.5 mmol) and potassium carbonate (2.59 g; 18.8 mmol) in DMF (40 ml). The batch was stirred at 85° C. overnight. After cooling, the batch was filtered over celite and concentrated in vacuo. The residue was taken up in ethyl acetate and washed with water (2×) and saturated aqueous sodium chloride solution (2×). The organic phase was dried (sodium sulfate), filtered and concentrated. The residue was purified by chromatography (hexane/ethyl acetate 8:2) to give the desired product (2.38 g; 11.4 mmol).

1. temperaturecooled to 0° C
2. stirringunder stirring
3. stirringThe batch was stirred for 30 minutes at 50° C.
4. temperaturecooled to 0° C. again
5. stirringunder stirring
6. stirringthe batch was stirred for 10 minutes
7. customThe organic phase was separated
8. extractionthe aqueous phase was extracted with diethyl ether (2×)
9. washThe combined organic phases were washed with saturated aqueous ammonium chloride solution (2×), aqueous sodium bicarbonate solution (5%, 2×), water (2×) and saturated aqueous sodium chloride solution (2×)
10. dry with materialThe organic phase was dried (magnesium sulfate)
11. filtrationfiltered before it
12. stirringThe batch was stirred at 85° C. overnight
13. temperatureAfter cooling
14. filtrationthe batch was filtered over celite and
15. concentrationconcentrated in vacuo
16. washwashed with water (2×) and saturated aqueous sodium chloride solution (2×)
17. dry with materialThe organic phase was dried (sodium sulfate)
18. filtrationfiltered
19. concentrationconcentrated
20. customThe residue was purified by chromatography (hexane/ethyl acetate 8:2)

ORD record

ord-ee401e6e40be4bae8f465a137acc4fe2

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133171B2