Hydrochloric Acid → (5-(Benzyloxy)pyridin-3-yl)boronic acid

HRID 1877476

Reaction equation

Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=1.[B:16](OC(C)C)([O:21]C(C)C)[O:17]C(C)C.C([Li])CCC.Cl>C1(C)C=CC=CC=1.O1CCCC1>[CH2:9]([O:8][C:6]1[CH:7]=[C:2]([B:16]([OH:21])[OH:17])[CH:3]=[N:4][CH:5]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: -70 °C

Procedure

1.91 g of 3-bromo-5-benzyloxypyridine, under argon, are added to a solution of 2 ml of triisopropyl borate in a mixture of 12 ml of toluene and 3 ml of tetrahydrofuran. The solution is cooled to −70° C. and then 5.42 ml of n-butyllithium (1.6N in hexane) are added dropwise. The reaction medium is stirred for 3 hours, and brought back to −20° C., and 7.23 ml of 2N hydrochloric acid are added dropwise. The reaction mixture is left to return to ambient temperature and poured into distilled water. The aqueous phase is extracted with ethyl acetate, and then the organic phase is washed with a saturated solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure, so as to give 0.21 g of [5-(benzyloxy)pyridin-3-yl]boronic acid in the form of a white powder (adapted from Wenjie Li et al. An Improved Protocol for the Preparation of 3-Pyridyl- and Some Arylboronic Acids J. Org. Chem., (2002), 67(15), 5394-5397), the characteristics of which are the following:

Workup

custombrought back to −20° C.
waitThe reaction mixture is left
customto return to ambient temperature
additionpoured
distillationinto distilled water
extractionThe aqueous phase is extracted with ethyl acetate
washthe organic phase is washed with a saturated solution of sodium chloride
dry with materialdried over magnesium sulphate
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-d601ff0e341248eba784433b0aeaddd8
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309721B2

Linked notes

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