Triethylamine → HCID 15341318, compound

A solution of 19.0 ml (218 mmol) of oxalyl chloride in 250 ml of dichloromethane was cooled in a dry ice-methanol bath. A solution of 27.0 ml (380 mmol) of dimethyl sulfoxide in 90 ml of dichloromethane was dropped into the above solution in 10 minutes at such a rate that the bulk temperature was kept within the range of -60° to -50° C. The obtained mixture was further stirred for 4 minutes to give a colorless solution. A solution of 31.92 g (151 mmol) of the 2-(4-nitroimidazol-1-yl)cyclohexanol prepared in the Preparative Example 11 in a mixture comprising 240 ml of dichloromethane and 30 ml of dimethyl sulfoxide was dropped into the colorless solution in 7 minutes at such a rate that the bulk temperature did not exceed -50° C. The obtained mixture was further stirred for 15 minutes. 80.0 ml (570 mmol) of triethylamine was dropped into the resulting mixture in 7 minutes at such a rate that the bulk temperature did not exceed -50° C. The obtained mixture was further stirred for 7 minutes and thereafter the dry ice-methanol bath was taken off. After 30 minutes, the bulk temperature reached +10° C. A saturated aqueous solution of sodium hydrogencarbonate was added to the resulting mixture and the obtained mixture was left standing to cause liquid-liquid separation. The organic phase was concentrated in a vacuum and the obtained residue was dissolved in ethyl acetate. Further, the aqueous phase was extracted with ethyl acetate and the ethyl acetate phase was combined with the ethyl acetate solution prepared above. The obtained mixture was washed with a saturated aqueous solution of common salt. The organic phase was dried over anhydrous magnesium sulfate and concentrated in a vacuum to give 33.9 g of a crude crystal. This crude crystal was recrystallized from dichloromethane/ethyl acetate to give 26.53 g of the title compound as a colorless crystal. Further, the mother liquor was recrystallized from dichloromethane/diisopropyl ether to give 2.52 g of the title compound as a lightly yellowish-brown crystal. Thus, 29.05 g of the title compound was obtained in total (yield: 92%).

1. customwas kept within the range of -60° to -50° C
2. customto give a colorless solution
3. additionwas dropped into the colorless solution in 7 minutes at such a rate that the bulk temperature
4. customdid not exceed -50° C
5. stirringThe obtained mixture was further stirred for 15 minutes
6. customdid not exceed -50° C
7. stirringThe obtained mixture was further stirred for 7 minutes
8. waitAfter 30 minutes
9. customreached +10° C
10. waitthe obtained mixture was left
11. customliquid-liquid separation
12. concentrationThe organic phase was concentrated in a vacuum
13. dissolutionthe obtained residue was dissolved in ethyl acetate
14. extractionFurther, the aqueous phase was extracted with ethyl acetate
15. customprepared above
16. washThe obtained mixture was washed with a saturated aqueous solution of common salt
17. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
18. concentrationconcentrated in a vacuum
19. customto give 33.9 g of a crude crystal
20. customThis crude crystal was recrystallized from dichloromethane/ethyl acetate

ORD record

ord-a29fc767d99f41ccb5edb53cc1e99be6

Source dataset

uspto-grants-1995_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05444066