2-Bromopropane → 6-Chloro-4-(3-chloro-phenyl)-2-isopropoxy-quinoline-3-carboxylic acid tert-butyl ester

Temperature

25 °C

To the stirred solution of 6-chloro-4-(3-chloro-phenyl)-2-hydroxy-quinoline-3-carboxylic acid tert-butyl ester (prepared as described in example 91 step B, 400 mg, 1.02 mmol) in 8 ml DMF was added NaH (60%, 65 mg, 1.54 mmol) portion wise at 0° C. and the resulting reaction mixture was stirred for 30 min at 25° C. Then the reaction mixture was cooled to 0° C. and a solution of 2-bromo-propane (0.192 ml, 2.05 mmol) was added dropwise in 2 ml DMF. The reaction mixture was stirred for 16 h at 50° C. and then quenched with saturated aqueous ammonium chloride solution (10 ml). Subsequently the mixture was diluted with water (25 ml) and extracted with ethyl acetate (3×60 ml). The organic phases were combined and was washed with brine (25 ml), dried over sodium sulfate and concentrated in vacuo to give a crude residue which was purified by column chromatography eluting with 2% ethyl acetate in hexane to yield 6-chloro-4-(3-chloro-phenyl)-2-isopropoxy-quinoline-3-carboxylic acid tert-butyl ester (290 mg, 65% yield) as an off white solid. LC-MS (ESI): 432 (M+H)+.

1. customthe resulting reaction mixture
2. temperatureThen the reaction mixture was cooled to 0° C.
3. stirringThe reaction mixture was stirred for 16 h at 50° C.
4. customquenched with saturated aqueous ammonium chloride solution (10 ml)
5. additionSubsequently the mixture was diluted with water (25 ml)
6. extractionextracted with ethyl acetate (3×60 ml)
7. washwas washed with brine (25 ml)
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated in vacuo
10. customto give a crude residue which
11. customwas purified by column chromatography
12. washeluting with 2% ethyl acetate in hexane

ORD record

ord-a5862ed724a24a83b4fa8c67ba7b7466

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09199938B2