Potassium Hydroxide → cis-4-Amino-6-hydroxy-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

To a stirred solution of 6-benzyloxy-4-hydroxyimino-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (2.05 g, 5.33 mmol), in ethanol (20 mL) and aqueous 2N KOH (16 mL, 32 mmol) was added aluminum-nickel alloy (1.82 g, 50% Ni, 21.2 mmol) in portions. The reaction was stirred at room temperature for 1.5 h, then additional aluminum-nickel alloy (1.82 g, 21.2 mmol) was added, and the reaction was stirred for 3 h. Additional aqueous 2N KOH (20 mL, 40 mmol) was added, and the reaction was stirred for 1 h. The mixture was then filtered through a bed of Celite®, rinsing with ethyl acetate. The filtrate was concentrated in vacuo, and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give 0.65 g crude product. Purification by silica gel chromatography using 0-5% methanol/dichloromethane as eluent afforded 387 mg of the title compound (26%).

1. stirringthe reaction was stirred for 3 h
2. stirringthe reaction was stirred for 1 h
3. filtrationThe mixture was then filtered through a bed of Celite®
4. washrinsing with ethyl acetate
5. concentrationThe filtrate was concentrated in vacuo
6. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
7. washThe combined organic phases were washed with brine (30 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give 0.65 g crude product
12. customPurification by silica gel chromatography

ORD record

ord-35c4955ebe214e6aa0fd8d97df7f5526

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06362198B1