4,4,4-Trifluorobutanal → (1RS)-4,4,4-Trifluoro-1-(7-methoxyquinolin-3-yl)butan-1-ol

Temperature

-78 °C

BuMgCl (0.16 mL of a 2 M solution in ether, 0.32 mmol) was added to 1 mL of toluene at −10° C. n-BuLi (0.26 mL of a 2.5 M solution in hexanes, 0.64 mmol) was added dropwise and the reaction mixture was allowed to age at −10° C. for 45 min. A solution of 3-bromo-7-methoxyquinoline (200 mg,) in 1 mL of toluene was added at −20° C. After 1 h, the reaction mixture was cooled to −78° C. and 4,4,4-trifluorobutyraldehyde (0.16 mL, 1 mmol) was added and the reaction mixture was slowly allowed to warm to ambient temperature. The procedure was repeated proportionally using 440 mg (1.8 mmol) of 3-bromo-7-methoxyquinoline. The two reactions were combined and partitioned between water and hexanes-EtOAc. The organic phase was concentrated and purified by flash chromatography on silica gel (25% to 66% EtOAc/hexanes) to provide the title compound as a racemic mixture. 1H NMR (500 MHz, CD2Cl2): δ (ppm) 8.71 (d, J=2.1 Hz, 1H), 8.06 (s, 1H), 7.70 (d, J=8.9 Hz, 1H), 7.35 (d, J=2.1 Hz, 1H), 7.21 (dd, J=8.9, 2.2 Hz, 1H), 4.93 (m, 1H), 3.93 (s, 3H), 2.33 (m, 2H).

1. additionwas added dropwise
2. waitAfter 1 h
3. temperatureto warm to ambient temperature
4. custompartitioned between water and hexanes-EtOAc
5. concentrationThe organic phase was concentrated
6. custompurified by flash chromatography on silica gel (25% to 66% EtOAc/hexanes)

ORD record

ord-6ca17aa2a06d4fb38c530b60a2b19a94

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07935713B2