Diethyl Malonate → Diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate

Diethyl malonate (9.8 g, 1.1 eq.) was added to a stirred suspension of sodium hydride (60% in mineral oil, 2.09 g) in 88 mL DMF over 15 min. at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. A solution of 2-cyclopropylmethoxy-4-fluoro-1-nitrobenzene (10 g, 1 eq.) in DMF (88 mL) was added drop wise at 0° C., and the reaction mixture was heated to 100° C. for 3 h. The reaction mixture was allowed to cool to room temperature, poured into ice water and extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave 10.0 g of crude product which was purified by silica gel chromatography (hexane/EtOAc) gave 7.0 g of the desired product (42%)

1. temperaturethe reaction mixture was heated to 100° C. for 3 h
2. temperatureto cool to room temperature
3. extractionextracted with EtOAc (3×100 mL)
4. washThe combined organic phases were washed with water (3×100 mL), brine (100 mL)
5. dry with materialdried (MgSO4)
6. customEvaporation of solvent under reduced pressure
7. customgave 10.0 g of crude product which
8. customwas purified by silica gel chromatography (hexane/EtOAc)

ORDレコード

ord-a78fdd8382ea4fe1bbf5c352cd325dd4

出典データセット

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08664249B2