Sodium hydride → HCID 70976335, compound

Temperature

160 °C

A mixed liquid containing diethyl 4-bromobenzylmalonate (9.88 g, 30.0 mmol) and anhydrous N,N-dimethylformamide (12.0 mL) was added gradually at 0° C. to a mixed liquid containing sodium hydride (62 wt % in oil, 1.74 g, 45 mmol) and anhydrous N,N-dimethylformamide (18.0 mL). Following stirring of the resulting mixed liquid at this temperature for 30 minutes, a mixed liquid containing 4-iodobenzyl bromide (11.6 g, 39.0 mmol) and anhydrous N,N-dimethylformamide (30 mL) was added. The resulting mixed liquid was stirred at room temperature for 3 hours, and a saturated aqueous solution of ammonium chloride was then added to halt the reaction. The organic layer was separated from the mixed liquid, and the water layer was extracted with ethyl acetate. The thus obtained organic layer was washed with a saturated saline solution and then dried using anhydrous magnesium sulfate. The organic layer was filtered, the filtrate was concentrated under reduced pressure, to the thus obtained residue were added lithium chloride (5.09 g, 120 mmol), water (1.08 mL) and N,N-dimethylformamide (100 mL), and the resulting mixture was heated for 12 hours at 160° C. The thus obtained mixed liquid was cooled to room temperature, water (100 mL) was added, and the mixture was extracted with ethyl acetate. The thus obtained organic layer was dried using anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:1), yielding the title compound (4h) (11.9 g, 25.2 mmol) as a yellow liquid in a yield of 84%.

1. additionwas added gradually at 0° C. to a mixed liquid
2. additionmixed liquid at this temperature for 30 minutes
3. additionwas added
4. additionThe resulting mixed liquid
5. stirringwas stirred at room temperature for 3 hours
6. customthe reaction
7. customThe organic layer was separated from the mixed liquid
8. extractionthe water layer was extracted with ethyl acetate
9. washThe thus obtained organic layer was washed with a saturated saline solution
10. customdried
11. filtrationThe organic layer was filtered
12. concentrationthe filtrate was concentrated under reduced pressure, to the thus obtained residue
13. customThe thus obtained
14. additionmixed liquid
15. temperaturewas cooled to room temperature
16. extractionthe mixture was extracted with ethyl acetate
17. customThe thus obtained organic layer was dried
18. filtrationfiltered
19. concentrationThe filtrate was concentrated under reduced pressure
20. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:1)

ORD record

ord-93e8642c16774cf4aaceb413b310bbff

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051246B2