Sodium hydride → HCID 67988326, compound

Temperature

-10 °C

To a −10° C. cold yellow solution of 5-chloro-2-nitroaniline (8.00 g, 46.36 mmol) in dry DMF (130 ml) was added sodium hydride 60% (9.27 g, 231.79 mmol) under Ar. The resulting red suspension was stirred at −10° C. for 10 minutes. A solution of 1-benzofuran-2-sulfonyl chloride (12.05 g, 55.63 mmol) in dry DMF (50 ml) was added dropwise with a dropping funnel at −10° C. (10 minutes of addition, exothermic reaction, maximum temperature of addition was 0° C., 5 ml of DMF to rinse the funnel). The resulting orange suspension was stirred at −10° C. for 30 minutes (color changed to brown). The reaction mixture was quenched with half saturated NaHCO3 solution (400 ml) and the product was extracted five times with EtOAc (1×650 ml and 4×300 ml). The combined organic layers were dried over Na2SO4, filtered and the filtrate evaporated to dryness. The crude product was combined with the crude product of an analogously performed 8 g scale attempt to give 61.82 g of an orange oil which was purified by MPLC (crude was dissolved in CH2Cl2/MeOH, preabsorption on silica gel, column D, program 3, 5 runs) to afford Intermediate 4 (28.91 g, 88% yield based on combined starting material) as yellow solid.

1. addition10 minutes of addition, exothermic reaction, maximum temperature of addition
2. customwas 0° C.
3. wash5 ml of DMF to rinse the funnel)
4. stirringThe resulting orange suspension was stirred at −10° C. for 30 minutes (color changed to brown)
5. customThe reaction mixture was quenched with half saturated NaHCO3 solution (400 ml)
6. extractionthe product was extracted five times with EtOAc (1×650 ml and 4×300 ml)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. customthe filtrate evaporated to dryness

ORD record

ord-12bf5d2f0a094748b096841a3e4aee83

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08729066B2