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

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Reaction Steps

1-Methylethyl {(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate (for a preparation see Intermediate 3) (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. Sodium borohydride (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), hydrochloric acid (1M, 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 min, MH+ 327

Provenance & Evidence