Hexane → (9-Fluoro-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)boronic acid

HRID 921971Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[N:8]1[C:13]([CH3:16])=[N:14][N:15]=[C:7]1[CH2:6][CH2:5]2.[Li]CCCC.CCCCCC.[B:28](OC(C)C)([O:33]C(C)C)[O:29]C(C)C>C1COCC1>[F:12][C:10]1[CH:11]=[C:2]([B:28]([OH:33])[OH:29])[CH:3]=[C:4]2[C:9]=1[N:8]1[C:13]([CH3:16])=[N:14][N:15]=[C:7]1[CH2:6][CH2:5]2

Participants

Conditions

Temperature: -78 °C

Procedure

7-Bromo-9-fluoro-4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-a]quinoline (1-5, 3.90 g, 13.8 mmol) was dissolved under nitrogen atmosphere in dry THF and cooled to −78° C. A 2.5 M n-BuLi solution in hexane (V=6.60 ml, 16.6 mmol) was added dropwise and stirred at −78° C. for 30 min. Triisopropyl borate (V=4.5 ml, 19.3 mmol) was added in one portion and the temperature raised to −50° C. for additional 30 min. The mixture was allowed to warm up to 0° C. and quenched with a 1M KHSO4 solution in order to reach pH 3. The solution was basified with a 2M NaOH solution and washed twice with ethyl acetate. The water layer was neutralized with conc. HCl and the precipitate was successively washed with water and ether and dried under reduced pressure to obtain the title compound as a white solid; MS (ESI): m/z=248.04 [M+H]+.

Workup

temperaturethe temperature raised to −50° C. for additional 30 min
temperatureto warm up to 0° C.
customquenched with a 1M KHSO4 solution in order
washwashed twice with ethyl acetate
washthe precipitate was successively washed with water and ether
customdried under reduced pressure

Sources & evidence

ORD record: ord-b6d5745ebd104bfd9187f059e470b350
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278093B2

Reaction notes

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