Sodium hydride → 2,2,2-Trifluoro-1-{6-methoxy-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-3,4-dihydro-1H-isoquinolin-2-yl}ethanone

A solution of 2,2,2-trifluoro-1-[1-(4-hydroxyphenyl)-6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethanone (18.98 g, 54.0 mmol) in anhydrous DMF (200 ml) was added to a suspension of NaH (2.592 g, 108.0 mmol) in anhydrous DMF (400 ml) at rt under N2. After stirring at rt for 1 hr, a solution of 1-(2-chloroethyl)pyrrolidine hydrochloride (9.184 g, 54.0 mmol) in anhydrous DMF (200 ml) was added and the reaction mixture was heated to 100° C. for 4 hr. The reaction mixture was cooled to rt, diluted with H2O (2000 ml), and extracted with EtOAc (4×250 ml). The combined extracts were washed with H2O (3×250 ml), dried over MgSO4, and concentrated in vacuo to give 21.15 g of yellow oil. Purification by flash chromatography, eluting with EtOAc:MeOH (8:2) gave 10.503 g (43% yield) of yellow oil.

1. temperaturethe reaction mixture was heated to 100° C. for 4 hr
2. temperatureThe reaction mixture was cooled to rt
3. extractionextracted with EtOAc (4×250 ml)
4. washThe combined extracts were washed with H2O (3×250 ml)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo

ORDレコード

ord-6cdbae25dc1e42ec8b1ace292ea04137

出典データセット

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06608203B2