Citric Acid → (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid

N-BOC-4-hydroxy-L-proline (A; 281 mg; 1.21 mmol) was dissolved in dimethylsulfoxide (3 mL) at room temperature then potassium t-butoxide (270 mg; 2.4 mmol) was added. The resulting solution was stirred at room temperature for 2 hours, then cooled to 0° C. A solution of 1-chloro-6-methoxy-3-methylisoquinoline in dimethylsulfoxide (3 mL) was then added dropwise to the cold solution, followed by t-BuOK, and the mixture was allowed to warn to room temperature. The solution was stirred for 16 hours. The reaction mixture was acidified to pH=4 with 5% aq. citric acid. The solution was extracted with ethyl acetate and the organic phase washed with water followed by brine. The organic phase was concentrated under reduced pressure to give (2S,4R)-1-(tert-butoxycarbonyl)-4-(6-methoxy-3-methylisoquinolin-1-yloxy)pyrrolidine-2-carboxylic acid.

1. temperaturecooled to 0° C
2. customto warn to room temperature
3. stirringThe solution was stirred for 16 hours
4. extractionThe solution was extracted with ethyl acetate
5. washthe organic phase washed with water
6. concentrationThe organic phase was concentrated under reduced pressure

ORD 기록

ord-c0d6882bdf8740b1b82840f7788649d4

출처 데이터셋

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08211897B2