Diethyl Malonate → Diethyl 2-(2,5-dichloro-4-methoxyphenyl)malonate

温度

100 °C

A solution of 1-bromo-2,5-dichloro-4-methoxybenzene (Intermediate 4-6; 3.82 g, 14.93 mmol), cesium carbonate (14.59 g, 44.78 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.427 g, 0.90 mmol) in toluene (220 mL) was thoughroughly degassed. The mixture was treated with diacetoxypalladium (0.101 g, 0.45 mmol) and diethyl malonate (2.505 mL, 16.42 mmol) and the resulting solution stirred under a nitrogen atmosphere at 100° C. for 18 hours. The reaction mixture was allowed to cool to ambient temperature, evaporated to dryness and partitioned between EtOAc (150 mL) and water (100 mL). The mixture was filtered and the aqueous layer was separated and re extracted with EtOAc (150 mL). The organic extracts were combined, dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford diethyl 2-(2,5-dichloro-4-methoxyphenyl)malonate (1.880 g, 37.6%) as a yellow oil.

1. temperatureto cool to ambient temperature
2. customevaporated to dryness
3. custompartitioned between EtOAc (150 mL) and water (100 mL)
4. filtrationThe mixture was filtered
5. customthe aqueous layer was separated
6. extractionre extracted with EtOAc (150 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customto afford crude product
11. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane
12. customPure fractions were evaporated to dryness

ORDレコード

ord-0d585eff1bc74209b30b86a66cc1c17c

出典データセット

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08188092B2