Citric Acid → Isopropyl ((2S,4R)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-YL)carbamate

1-Methylethyl {(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate (for a preparation see Intermediate 12) (17.9 g, 52.2 mmol) was taken up in ethanol (150 mL) and cooled to below −10° C. (internal temperature) in a CO2/acetone bath. NaBH4 (1.381 g, 36.5 mmol) was added followed by magnesium chloride hexahydrate (11.35 g, 55.8 mmol) in water (25 mL) keeping the temperature below −5° C. The mixture was allowed to stir at <0° C. for 1 h then warmed to room temperature and stirred for 1 h. The resulting thick suspension was poured into a mixture of citric acid (25.05 g, 130 mmol), HCl (1M in water, 205 mL, 205 mmol) and DCM (205 mL). The biphasic mixture was stirred at room temperature for 1 h. The layers were separated and the organic layer dried with Na2SO4, filtered and concentrated to yield the product as a light brown solid (14.1 g). LCMS (Method B): Rt=1.13, MH+=327

1. temperaturecooled to below −10° C. (internal temperature) in a CO2/acetone bath
2. customthe temperature below −5° C
3. stirringstirred for 1 h
4. stirringThe biphasic mixture was stirred at room temperature for 1 h
5. customThe layers were separated
6. dry with materialthe organic layer dried with Na2SO4
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-2177ac42574c4c22b886fe12d8db9bb4

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993554B2