Water → 7-Bromo-1,2,3,4-tetrahydroquinoline

Temperature

70 °C

BF3.Et2O (49.2 g, 56.7 mL, 346.2 mmol) was added to a solution of (Z)-6-bromo-2,3-dihydro-1H-inden-1-one O-triisopropylsilyl oxime (1D) (66 g, 173.1 mmol) in 400 mL of dry Et2O. Me2S.BH3 (31.5 g, 39.48 mL 415.5 mmol) was then added dropwise. The reaction mixture was heated to reflux for 48 hours (followed by TLC 100% petroleum ether until complete disappearance of starting material). The mixture was cooled to 0° and dropped to ice/water cautiously, followed by 60 mL of 1:1 solution of water/concentrated HCl. This reaction mixture was heated to 70° C. for 80 minutes and then allowed to cool to rt and stirred for 3.5 hours, washed with Et2O. The pH of the remaining aqueous phase was adjusted to pH>10 with 5M NaOH and extracted three times with Et2O. The combined organic phases were washed with brine and dried over K2CO3. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE:EtOAc (100:1) to provide 11.2 g (31%) of the desired product 7-bromo-1,2,3,4-tetrahydroquinoline (1E): 1H-NMR (DMSO-d6, 400 MHz): δ1.7 (m, 2H), 2.6 (m, 2H), 3.15 (m, 2H), 5.9 (s, 1H), 6.45 (m, 1H), 6.55 (m, 1H), 6.75 (m, 1H), LC/MS (APCI): m/z 211.7 (M+H).

1. additionBH3 (31.5 g, 39.48 mL 415.5 mmol) was then added dropwise
2. temperatureThe reaction mixture was heated
3. temperatureThe mixture was cooled to 0°
4. temperatureto cool to rt
5. washwashed with Et2O
6. extractionextracted three times with Et2O
7. washThe combined organic phases were washed with brine
8. dry with materialdried over K2CO3
9. customThe crude material was purified by column chromatography on silica gel eluting with a gradient of PE

ORD record

ord-b2dbaf86a23f4adea5f6edf6fcdf6a1e

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067928B2