Dimethylformamide → HCID 15341725, compound

Temperature

50 °C

Dimethylformamide (116 μL, 1.5 mmol, 0.1 eq.) and thionyl chloride (1.63 ml, 22.5 mmol, 1.5 eq.) were added to a solution of 5-bromovaleric acid (2.71 g, 15 mmol, 1 eq.) in toluene (20 ml) and the reaction mixture was stirred at 50° C. for 4 h. The volatiles were removed under high vacuum, THF (130 ml) was added and the mixture was cooled to 0° C. N,N-Diisopropylethylamine (4.2 ml, 24 mmol, 1.6 eq.) and ethylamine (2 M solution in THF, 9.0 ml, 18 mmol, 1.2 eq.) were added dropwise. The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml). The reaction mixture was extracted with Et2O (4×75 ml) and the combined organic phases were washed with brine (100 ml) before being dried (MgSO4), filtered, and concentrated to give the crude material. This was purified by flash chromatography, eluting with petrol/EtOAc (4:6), giving the title product 95 as a clear, colourless oil (2.75 g, 88%). Analytical data consistent with the literature (Halazy, S. et al., WO 9612713, Pierre Fabre Medicament (1996)).

1. customThe volatiles were removed under high vacuum, THF (130 ml)
2. additionwas added
3. temperaturethe mixture was cooled to 0° C
4. stirringThe reaction mixture was stirred for 1 h at 0° C.
5. custombefore being quenched by the addition of saturated aq. NH4Cl (100 ml)
6. extractionThe reaction mixture was extracted with Et2O (4×75 ml)
7. washthe combined organic phases were washed with brine (100 ml)
8. dry with materialbefore being dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto give the crude material
12. customThis was purified by flash chromatography
13. washeluting with petrol/EtOAc (4:6)

ORD record

ord-a8bb20b24c2b44fe8483b5535b43e731

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09242954B2